A conserved human population of TRAV26+ type II Natural Killer T cells solely recognise CD1d

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Abstract Most studies of CD1d-restricted Natural killer T cells (NKT) have focussed on type I TRAV10-TRAJ18 + NKT cells that recognise the glycolipid a-GalCer. Our understanding of type II NKT cells, their TCR gene usage and ligand diversity remains unclear. Here, using CD1d tetramers carrying diverse endogenous lipids (CD1d-endo), we identified public human TRAV26 + type II NKT TCRs present in all individuals, with many expressing a conserved TRAV26-2-TRAJ48 TCRa chain. Cellular, molecular and lipidomic analyses showed that TRAV26 + TCRs bound with similar affinities to CD1d loaded with diverse lipids, suggesting lipid-independent binding. Crystal structures of TRAV26 + TCR-CD1d complexes showed these TCRs bound solely to the A'-roof of CD1d, distant from the protruding lipid. Collectively we have uncovered a population of public lipid-independent TRAV26 + type II NKT cells, suggesting a potential role in diseases where aberrant CD1d expression occurs.
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A conserved human population of TRAV26+ type II Natural Killer T cells solely recognise CD1d | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A conserved human population of TRAV26 + type II Natural Killer T cells solely recognise CD1d Kean CY Poa, Christopher M Harpur, Tan-Yun Cheng, Elena Batleska, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7004764/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Most studies of CD1d-restricted Natural killer T cells (NKT) have focussed on type I TRAV10-TRAJ18 + NKT cells that recognise the glycolipid a-GalCer. Our understanding of type II NKT cells, their TCR gene usage and ligand diversity remains unclear. Here, using CD1d tetramers carrying diverse endogenous lipids (CD1d-endo), we identified public human TRAV26 + type II NKT TCRs present in all individuals, with many expressing a conserved TRAV26-2-TRAJ48 TCRa chain. Cellular, molecular and lipidomic analyses showed that TRAV26 + TCRs bound with similar affinities to CD1d loaded with diverse lipids, suggesting lipid-independent binding. Crystal structures of TRAV26 + TCR-CD1d complexes showed these TCRs bound solely to the A'-roof of CD1d, distant from the protruding lipid. Collectively we have uncovered a population of public lipid-independent TRAV26 + type II NKT cells, suggesting a potential role in diseases where aberrant CD1d expression occurs. Biological sciences/Immunology/Lymphocytes/T cells/NKT cells Biological sciences/Immunology/Antigen processing and presentation/Cellular immunity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION Natural Killer T (NKT) cells recognise lipid-based antigens (Ags) presented by the monomorphic MHC class I-like molecule CD1d. NKT cells are generally classified into two main groups, type I and II NKT cells 1 . Most studies have focussed on type I NKT cells, which express an evolutionary conserved public T cell receptor (TCR) repertoire in humans, defined by an invariant TRAV10-TRAJ18 + TCRα chain paired with TRBV25-1 + TCRβ chains, that confers co-recognition of a prototypical glycolipid Ag known as α-galactosylceramide (α-GalCer) and related hexosyl ceramides when bound to CD1d 2 , 3 . The use of CD1d-α-GalCer tetramers has enabled extensive research to characterise the phenotypic profile and function of type I NKT cells 1 , 2 . Type II NKT cells were identified circa 30 years ago in mice as CD4 + T cells that do not recognize MHC class II 4, 5 , or as CD1d-reactive cells that do not require CD1d recycling to endosomes 6 . Those studies suggested that type II NKT cells express diverse TCR genes, distinct from the semi-invariant TCR characteristic of type I NKT cells, and are therefore commonly described as ‘diverse’ NKT cells 1 . In contrast to type I NKT cells, type II NKT cells do not recognize α-GalCer but can be activated by other CD1d-bound lipid-based Ags including sulfatides and phospholipids as well as small molecules 2 , 5 , 7 . Type II NKT cells appear to play a unique role in the immune system 2 , with some studies in humans suggesting opposing roles to type I NKT cells 8 , 9 . Type II NKT cells are comprised of specialized subsets capable of monitoring biological processes that impact on lipid metabolism and consequently, on the self-lipids bound to CD1d 5 , 10 , 11 , 12 , 13 . These cells are associated with, or implicated in, various diseases such as hepatitis, ulcerative colitis, and cancer 8 , 9 . In humans, type II NKT cells appear to outnumber type I NKT cells 14 , 15 , 16 . However, the paucity of reagents to clearly identify type II NKT cells has left fundamental questions unanswered that include the identity of immunodominant Ags, TCR patterns, the underlying mechanisms that regulate their numbers and the molecular mechanism of Ags recognition 2 . Insights have been gained into the molecular mechanism that underpins the recognition of CD1d-lipid complexes by human and mouse type I NKT TCRs 17 , 18 as well as mouse type II NKT TCRs 19 , 20 , 21 and ‘atypical’ NKT cells 22 , 23 , 24 , 25 , 26 . These studies led to the fundamental principle that underscored the NKT TCR co-recognition paradigm of CD1d-lipid complexes whereby the NKT TCR contacted both CD1d and the presented Ag 3 . However, our understanding of the molecular mechanism that underpins the recognition of CD1d-lipid by human type II NKT TCRs remains less clear. Here, using human CD1d tetramers presenting endogenous lipids, we identify a population of public type II NKT cells that express a TRAV26 + TCRa chain. Lipidomic scanning of Ags contained within CD1d-TRAV26 + TCR complexes revealed a diverse array of lipids, and structural determination of the ternary complex showed that the TCR contacted CD1d in an Ag-independent manner. RESULTS Identification of human CD1d-endo-reactive NKT cells. Early studies suggested that type II NKT cells can recognise and respond to CD1d carrying endogenous lipids (CD1d-endo) 4 , 6 , 14 , 15 , 16 , 27 , 28 . Although some target lipid-Ags for type II NKT cells are known, the study of these cells has been hindered by a limited understanding of their target lipid repertoire. To further investigate the antigenic targets and diversity of human type II NKT cells, CD1d-endo tetramers were generated using glycosylation-deficient GnTI −/− Human Embryonic Kidney 293 (HEK293S) cells to express soluble CD1d ectodomains that incorporate a cellular cargo of endogenous lipids during synthesis 29 , 30 . These CD1d-endo tetramers stained over 0.1% of live CD3 + T cells within peripheral blood mononuclear cells (PBMCs) from healthy human donors, albeit with varied and often low mean fluorescence intensity (MFI) in many cases (Fig. 1 a and S1a). After one round of tetramer-associated magnetic enrichment (TAME) 31 using phycoerythrin (PE)-labelled CD1d-endo tetramers, the frequency of the CD1d-endo tetramer + amongst CD3 + T cells generally yielded more defined populations at proportions ranging up to 13% (Median (M) 0.92%, interquartile range (IQR) 0.3–1.9%), in contrast to PE-conjugated streptavidin (SAV-PE) negative controls where no clear population was identified ( Fig. S1 a ). However, it was possible that some of these frequencies may be impacted by non-TCR CD1d ligands such as CD36 family members 32 , as suggested by the enrichment of CD3 − cells capturing the CD1d-tetramer after TAME (Fig. 1 a and S1a-b). To minimise this, for many samples, we used a CD42b exclusion gate to exclude platelets which express high levels of CD36 and/or CD36 blocking antibody prior to staining of some samples. To confirm TCR-dependent CD1d-binding specificity, CD3 + CD1d-endo tetramer + cells were enriched using flow cytometric cell sorting and expanded in culture for 18–20 days and re-stained with CD1d-endo tetramers. The CD1d-endo tetramer + populations varied widely in frequency (0.035-100%) of CD3 + cells (Fig. 1 a) but often formed more distinct clusters (M = 0.84%, IQR = 0.2–8.4%), when compared to post-MACS enriched samples. This may be because the expanded cells were devoid of platelets or other cell types that, through cell adhesion and/or trogocytosis, may confer TCR-independent binding with CD1d-tetramers (Fig. 1 and S1a) 32 . CD1d-endo tetramer + cells included both αβ and γδ T cells, with γδ T cell frequencies varying widely in the 25 donors analysed. CD1d-endo-tetramer + αβ T cells in these cultures (Fig. 1 b) were skewed towards CD4 + single positive (SP) expression (M 80%, IQR 46–94%), although CD8 + SP and CD4 − CD8 − double negative (DN) populations were also detected at lower frequencies (Fig. 1 c). Conversely, the CD1d-endo tetramer – conventional T cells had similar frequencies of CD4 + SP and CD8 + SP T cells. By co-labelling expanded cells with CD1d-endo tetramer and CD1d-α-GalCer tetramer, many CD1d-binding cells (M 80%, IQR 39–95%) co-stained with both tetramers (Fig. 1 d). In the three donors shown, representative of 18 analysed this way, the staining pattern revealed distinct T cell clusters that likely reflected the oligoclonality of expanded NKT cells. Most, but not all, clusters showed a positive correlation for staining intensity by both tetramers, suggesting that binding to CD1d occurs regardless of the lipids within the CD1d cleft. The functional potential of expanded cells was also investigated. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, CD1d-endo tetramer + cells expressed tumour necrosis factor (TNF) and interferon-g (IFNg) (mean 66% and 26%, respectively (Fig. 1 e), and cytokine production was detected in both CD8 − and CD8 + cells ( Fig. S1 c ). While some CD1d-endo tetramer + cells co-produced these cytokines (mean 20%), some produced either one or the other (Fig. 1 e). IL-13 was only detected in a small subset of CD1d-endo tetramer + cells in some donors, in contrast to CD1d-endo tetramer − cells where IL-13 was more frequently detected (Fig. 1 e). Thus, type II NKT cell populations capable of producing pro-inflammatory cytokines are readily identified among human donors by CD1d-endo tetramers with no defined exogenously loaded antigen. TRAV26 TCR bias amongst human CD1d-endo-reactive T cells. To characterise the TCR repertoire of the populations labelled by CD1d-endo tetramers, single CD1d-endo tetramer + cells were index sorted from in vitro expanded cultures and their TCR sequences were determined 31 . Paired TCRα and TCRβ, or TCRδ and TCRγ chain-transcripts were determined for cells sorted as αβ T cells or γδ T cells (Tables 1 and 2 ). None of the sorted T cell clones contained the canonical TCR usage that define type I NKT TCRs. Instead, they exhibited a varied, yet biased, range of γδ and αβ TCR chains (Fig. 2 a-b and Tables 1 and 2 ). Almost all γδ TCRs analysed incorporated TRDV1 genes (17 of 18 Vδ sequences derived from 11 donors (Table 1 ), in line with previous studies that described Vd1 + γδ T cells recognizing CD1d 22 , 23 , 33 and CD1c 34 . Unexpectedly, within the αβ TCRs, there was a strong bias towards TRAV26 + TCRs, with ~ 65% of αβ TCRs within CD1d-endo tetramer + cells from 11 donors utilising TRAV26- 2 gene segments. In addition, cells from 5 donors also utilised TRAV26-1 , which differs from TRAV26-2 by four germline encoded amino acids, as well as one amino acid in the CDR3α loop (Fig. 2 a and Table 2 ). Further, TRAV26-2 gene segments were often associated with TRAJ48 in 17 of 39 TCRs (Fig. 2 a and Table 2 ), although other TRAJ gene-rearrangements were also detected, including TRAJ42 in 6 of 39 TCRs, TRAJ23 in 5 of 39 TCRs and TRAJ45 in 4 of 39 TCRs (Fig. 2 a and Table 2 ). Type II NKT cells possessing TRAJ48 genes almost exclusively rearranged with TRAV26 + , with 17 encoded by TRAV26-2 and one by TRAV26-1 . Moreover, a conserved CDR3α involving the insertion of the same amino acid (G in position 6) in the N-region during rearrangements between TRAV26-2 and TRAJ48 genes was identified in 5 donors across 5 independent experiments (Fig. 2 b and Table 2 ), demonstrating public conservation of the CDR3a sequence. Notably, this same TRAV26-2–TRAJ48 rearrangement had also been reported in a single NKT cell clone isolated via a different approach 25 . Another conserved motif was detected in positions 6 and 7 of the TRAV26-2 CDR3a sequences, where proline was also often seen at position 6, typically accompanied by bulky residue at position 7 (Fig. 2 b and Table 2 ). In contrast to the conserved TCRα chain, the TCRβ gene usage was highly diverse, as were the CDR3β sequences and lengths (Table 2 ). Table 1 Paired gd TCR sequences of CD1d-endo tetramer + single-sorted cells IMGT TCR gene nomenclatures and associated complementary determining region (CDR) loop amino acid sequences are shown for γδ T cells sorted with CD1d-endo tetramers post-sort/expansion in culture for 21 d as per Fig. 1 a. The number of observations (obs. column) as well as intra-donor frequency at which each unique clonotype was observed amongst total amplified gd TCRs are shown from an analysis of 11 donors. A total of three sorting experiments were performed. Red residues are either partially or fully non-germline encoded. XX means undetermined. Sequences selected to generate γδ TCR-transduced NKT cell clones, are given a clone name. Amino acid positions: CDR1-IMGT (27 to 38), CDR2-IMGT (56 to 65), and CDR3 (105 to 117) Clone Donor TRDV TRDJ TRDD CDR1d CDR2d CDR3d (non germline) TRGV TRGJ CDR1g CDR2g CDR3g (non germline) Obs % within donor VD3G8 C4 TRDV3*01 TRDJ2*01 TRDD3*01 TVYS…NPD GDN…SRS CAF RGTGGYPWA AQLFF TRGV8*01 TRGJ2* VEN…AVY YDSY…NSRV CATW I YYKKLF 16 100 C3 TRDV1*01 TRDJ1*01 TRDD2*01 TSWW…SYY QG…S CALGE LLYPI TDKLIF - 6 100 C1 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE LRVGWGR LIF TRGV5*01 TRGJ1*02 VIN…AFY YDVS…NSKD CAT XXXX YKKLF 6 100 CA1 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE LAFFT TDKLIF TRGV8*01 TRGJ1/2*01 VEN…AVY YDSY…NSRV CAT RSR NYYKKLF 3 100 CA2 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE SGIRLY TDKLIF TRGV8*01 TRGJP1*01 VEN…AVY YDSY…NSRV CATWDR PGN TTGWFKIF 2 100 CA3 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE QVVYWGIRTM TDKLIF TRGV5*01 TRGJP2*01 VIN…AFY YDVS…NSKD CATWD SPPG SDWIKTF 7 47 CA3 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE LPGGYAG LIF TRGV4*01 TRGJ1*01 EGS…TGY YGSY…TSSV CAT PIPGVS KLF 8 53 CA4 TRDV1*01 TRDJ1*01 TRDD2/TRDD3*01 TSWW…SYY QG…S CALG DPASYPFVLGD TDKLIF TRGV5*01 TRGJP2*01 VIN…AFY YDVS…NSKD CATWD SPPG SDWIKTF 3 60 CA4 TRDV1*01 TRDJ1*01 TRDD2/TRDD3 TSWW…SYY QG…S CALG DPASYPFVLGD TDKLIF - 2 40 G58 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE SRTGGYARG KLIF TRGV4*01 TRGJ1*02/ TRGJ2*01 EGS…TGY YGSY…TSSV CATWD PVLN YKKLF 1 33 G58 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALG DSRRDKAY TDKLIF TRGV5*01 TRGJ1*01/ TRGJ2*01 VIN…AFY YDVS…NSKD CATWD GAQ LF 2 66 G59 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALG DPGVTH TDKLIF TRGV3*01 TRGJ1*02/ TRGJ2*01 VTN…TFY YDVS…TARD CATWDR LGAD KKLF 2 66 G59 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE RRIRGVN TDKLIF TRGV2*01 TRGJ1*02/ TRGJ2*01 EGS…NGY YDSY…NSKV CATWDG RG KLF 1 33 G60 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE NGYWG TDKLIF TRGV3*01 TRGJ1*02/ TRGJ2*01 VTN…TFY YDVS…TARD CATW PYP YKKLF 2 66 G60 TRDV1*01 TRDJ2*01 TRDD3*01 TSWW…SYY QG…S CALGE LRVLGA LTAQLFF TRGV4*01 TRGJ1*02/ TRGJ2*01 EGS…TGY YGSY…TSSV CATWD GLQKGS YKKLF 1 33 G62 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALGE TSYGGTGGYGVD TDKLIF - 1 33 G62 TRDV1*01 TRDJ1*01 TRDD2*01 TSWW…SYY QG…S CALGE RYLPTA DKLIF TRGV9*01 TRGJ1*02/ TRGJ2*01 GITI…SATS ISYD…GTV CALWE E YKKLF 1 33 G62 TRDV1*01 TRDJ1*01 TRDD3*01 TSWW…SYY QG…S CALG GLIYKGDSASLGG TDKLIF - 1 33 Table 2 Paired ab TCR sequences of CD1d-endo tetramer + single-sorted cells IMGT TCR gene nomenclatures and associated complementary determining region (CDR) loop amino acid sequences are shown for ab T cells sorted with CD1d-endo tetramers post-sort/expansion in culture for 21 d as per Fig. 1 a. The number of observations (obs. column) as well as intra-donor frequency at which each unique clonotype was observed amongst total amplified ab TCRs are shown from an analysis of 14 donors. Sequences in bold contain the invariant TRAV26-TRAJ48 rearrangement. A total of eight single-cell sorting experiments were performed. Red residues are either partially or fully non-germline encoded. Sequences selected to generate αβ NKT cell clones are given a clone name. Amino acid positions: CDR1-IMGT (27 to 38), CDR2-IMGT (56 to 65), and CDR3 (105 to 117). Clone Donor TRAV TRAJ CDR1a CDR2a CDR3a (non germline) TRBV TRBJ TRBD CDR1b CDR2b CDR3b (non germline) Obs % within donor iT26 4A TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILRD G FGNEKLTF TRBV6-2*01 TRBJ2-1*01 TRBD1*01 MNH…EY SVG…EGT CASSY QNKGF NEQFF 39 65 4A TRAV26-1*01 TRAJ44*01 TISG…NEY GLK…NN CIVR ASWR TGTASKLTF - 1 1.7 4A TRAV4*01 TRAJ13*01 NIAT…NDY GYK…TK CL GPL NSGGYQKVTF TRBV28-1*01 TRBJ1-1*01 TRBD1*01 MDH…EN SYD…VKM CASS FTGGAEGF EAFF 1 1.7 4A TRAV13-1*01 or TRAV13-2*01 TRAJ9*01 DSA…SNY IRSN…VGE CA VS NTGGFKTIF TRBV5-5*01 TRBJ1-1*01 TRBD1*01 SGH…KS YYE…KEE CASSL GGTVL NTEAFF 1 1.7 NSA…SDY IRSN…MDK CA 4A TRAV8-2*01 TRAJ49*01 SSY…SPS YTSA…ATLV CVVS GG TGNQFYF TRBV4-1*01 TRBJ2-1*01 TRBD2*01 MGH…RA YSY…EKL CASSQ DPSGRY EQFF 17 28.3 4A TRAV27*01 TRAJ23*01 SVF…SS VVTG…GEV CAG VS IYNQGGKLIF TRBV4-2*01 TRBJ2-1*01 TRBD1*01 LGH…NA YNF…KEQ CASSQ ERXA YNEQFF 1 1.7 4G TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CIL SSG FGNEKLTF TRBV4-1*01 TRBJ2-5 TRBD2*01 MGH…RA YSY…EKL CASS LPRLAGGA ETQYF 2 10 4G TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILRD G FGNEKLTF TRBV5-6*01 TRBJ2-6*01 TRBD1*01 SGH…DT YYE…EEE CASSL GTTP SGANVLTF 5 25 4G TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILRD GFM NYGGSQGNLIF TRBV19*01 TRBJ1-5*01 TRBD2*01 LNH…DA SQI…VND CAS TKVGGLSE PQHF 5 25 4G TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILR APF NFGNEKLTF TRBV28*01 TRBJ1-2*01 TRBD2*01 MDH…EH SYD…VKM CASSL NTPGG GYTF 3 15 4G TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILR F NYGGSQGNLIF - 1 5 4G TRAV26-2*01 TRAJ45*01 TISG…TDY GLT…SN CILRD GFSV YSGGGADGLTF - 4 20 4K TRAV26-1*01 TRAJ48*01 TISG…NEY GLK…NN CIVRV VV FGNEKLTF TRBV6-1*01 TRBJ1-2*01 TRBD1*01 MNH…NS SAS…EGT CASS PGWTGP NYGYTF 37 58.7 C3 TRAV26-1*01 TRAJ41*01 TISG…NEY GLK…NN CI G NSGYALNF TRBV6-2*01 TRBJ2-7*01 TRBD2*01 MNH…EY SVG…EGT CASS PGGXXE YEQYF 1 1.6 C3 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CIL GAPY NFGNEKLTF TRBV6-5*01 TRBJ2-7*01 TRBD1*01 MNH…EY SVG…AGI CASSY RGN EQYF 8 12.7 C3 TRAV26-2*01 TRAJ23*01 TISG…TDY GLT…SN CILRD GFE IYNQGGKLIF TRBV20-1*01 TRBJ2-6*01 TRBD1*01 DFQ…ATT SNEG…SKA CSA ARLEGP GANVLTF 1 1.6 C3 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILR PGF FGNEKLTF TRBV7-2*01 TRBJ2-5*01 TRBD2*01 SGH…TA FQG…NSA CASSL ASPGAXVV ETQYF 1 1.6 C3 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CI NQVY NFGNEKLTF TRBV12-4*01 TRBJ2-2*01 TRBD1*01 SGH…DY FNN…NVP CASS FITGG LFGELFF 9 14.3 C3 TRAV10*01 TRAJ17*01 VSP…FSN MTFS…ENT CVVS AG AAGNKLTF TRBV4-1*01 TRBJ2-4*01 TRBD2*01 MGH…RA YSY…EKL CASSQ GG AKNIQYF 5 7.9 C3 TRAV29/DV5*01 TRAJ54*01 NSM…FDY ISSI…KDK CAAS PI IQGAQKLVF - 1 1.6 C4 TRAV26-2*01 TRAJ32*01 TISG…TDY GLT…SN CILRD FGG NYGGATNKLIF TRBV27*01 TRBJ2-2 UNCLEAR 2 13.3 T26B C4 TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILRD GFK NYGGSQGNLIF TRBV13-1*01 TRBJ2-7*01 TRBD2*01 PRH…DT FYE…KMQ CASSL EGL YEQYF 6 40 T26A C4 TRAV26-2*01 TRAJ40*01 TISG…TDY GLT…SN CILRD GWG GTYKYIF TRBV19-1*01 TRBJ2-7*01 TRBD1*01 LNH…DA SQI…VND CA TSVGRP YEQYF 2 13.3 C4 TRAV26-2*01 TRAJ29*01 TISG…TDY GLT…SN CILRD GW SGNTPLVF - 4 26.7 C4 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILR NFGNEKLTF TRBV24-1*01 TRBJ1-1*01 TRBD1*01 KGH…DR SFD…VKD CATS EDXLGW TEAF 1 6.7 CA1 TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILRD GFE NYGGSQGNLIF TRBV20-1*01 TRBJ1-2*01 TRBD2 DFQ…ATT SNEG…SKA CSA RDREGA YGYTF 4 44.4 CA1 TRAV26-2*01 TRAJ23*01 TISG…TDY GLT…SN CILRD GFM IYNQGGKLIF - 1 11.1 CA1 TRAV26-2*01 TRAJ36*01 TISG…TDY GLT…SN CILR NPL TGANNLFF TRBV30*01 TRBJ1-6*01 TRBD1 GTS…NPN SVG…IG CAWS VAGGVIA SYNSPLHF 1 11.1 CA1 TRAV26-2*01 TRAJ54*01 TISG…TDY GLT…SN CILRD GFGKF QGAQKLVF - 3 33.3 CA2 TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILRD GWA NYGGSQGNLIF - 3 100 CA3 TRAV26-2*01 TRAJ30*01 TISG…TDY GLT…SN CILRD PL DDKIIF - 6 85.7 CA3 TRAV29/DV5*01 TRAJ48*01 NSM…FDY ISSI…KDK CAAS PTIS NFGNEKLTF - 1 1.6 CA4 TRAV14/DV4*01 TRAJ43*01 TSDQ…SYG QGSY…DEQN CAMRE G NNDMRF TRBV2*01 TRBJ2-7*01 TRBD2 SNH…LY FYN…NEI CASSE GLAGA YEQYEF 2 25 CA4 TRAV38-2/DV8*01 TRAJ33*01 TSES…DYY QEAY…KQQN CA M DSNYQLIW TRBV24-1*01 TRBJ2-1*01 TRBD2 KGH…DR SFD…VKD CATS APARLD NEQFF 2 25 CA4 TRAV35*01 TRAJ34*01 SIF…NT LYKA…GEL CA ST SYNTDKLIF TRBV28*01 TRBJ2-5*01 TRBD1*01 MDH…EN SYD…VKM CASS DLTGQG ETQYF 2 25 CA4 TRAV38-2/DV8*01 TRAJ52*01 TSES…DYY QEAY…KQQN CA YP NAGGTSYGKLTF - 2 25 CH5 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CIL QAPFN FGNEKLTF TRBV10-3 TRBJ1-1*01 TRBD2*01 ENH…RY SYG…VKD CAISE SSAAGR TEAF 19 25.7 CH5 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILR APL NFGNEKLTF TRBV19*01 TRBJ2-2*01 TRBD1*01 LNH…DA SQI…VND CASS NHRVGW TGELFF 13 17.6 CH5 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CIRLD G FGNEKLTF TRBV19*01 TRBJ2-7 TRBD1*01 LNH…DA SQI…VND CASS RGDRP YEQYEF 15 20.3 CH5 TRAV26-2*01 TRAJ34*01 TISG…TDY GLT…SN CILRD PWD TDLKIF TRBV3-1 TRBJ2-2*01 TRBD1*01 LGH…DT YNN…KEL CASSQ QTAT NTGELFF 11 14.9 CH5 TRAV29*01 TRAJ26*01 NSM…FDY ISSI…KDK CAAS EILK GQNFVF TRBV20-1*01 TRBJ2-1*01 TRBD2 DFQ…ATT SNEG…SKA CSA SYSAGHW NEQFF 8 10.8 CH5 TRAV17*01 TRAJ11*01 TSI…NN IRSN…ERE CATD TT GYSTLTF TRBV4-2*01 5 6.8 CH5 TRAV26-1*01 TRAJ37*01 TISG…NEY GLK…NN CIVRV F NTGKLIF - TRBJ2-7*01 TRBD2 LGH…NA YNF…KEQ CASSQ ADF SYEQYEF 3 4.1 CH7 TRAV26-1*01 TRAJ20*01 TISG…NEY GLK…NN CIVRV APPF NDYKLSF TRBV6-1*01 2 8.3 CH7 TRAV26-2*01 TRAJ43*01 TISG…TDY GLT…SN CILRD GFGL NNDMRF TRBV10-2*01 TRBJ1-1*01 TRBD1*01 MNH…NS SAS…EGT CASS RFPW NTEAF 12 50 CH7 TRAV26-2*01 TRAJ23*01 TISG…TDY GLT…SN CILRD PL IYNQGGKLIF TRBV14*01/*02 TRBJ2-7*01 TRBD1*01 WSH…SY SAA…ADI CASSE RLARY YEQYF 6 25 CH7 TRAV26-2*01 TRAJ45*01 TISG…TDY GLT…SN CILRD GFRVY YSGGGADGLTF TRBV9*02 TRBJ2-3*01 TRBD1*01 SGH…DN FVK…ESK CASS LRDRVWRKEG TDTQYF 2 8.3 CH7 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CIL GAPG FGNEKLTF - TRBJ2-3*01 TRBD1*01 SGD…LS YNN…GEE CASS VAPGPAK STDTQYF 1 4.2 CH7 TRAV26-2*01 TRAJ23*01 TISG…TDY GLT…SN CILRD PL IYNQGGKLIF - 1 4.2 CH8 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILRD G FGNEKLTF TRBV27*01 1 2.4 CH8 TRAV26-2*01 TRAJ57*01 TISG…TDY GLT…SN CILRD GWGLV TQGGSEKLVF TRBV9*01 TRBJ1-1*01 TRBD1*01 MNH…EY SMN…VEV CAS TPFRTGWS EAFF 13 31 CH8 TRAV26-2*01 TRAJ42*01 TISG…TDY GLT…SN CILRD GFS NYGGSQGNLIF TRBV27*01 TRBJ1-1*01 TRBD1*01 SGD…LS YNN…GEE CASS GLRDH EAFF 27 64.3 CH8 TRAV41*01 TRAJ49*01 VGI…SA LSS…GK CAV PSV GNQFYF - TRBJ2-7*01 TRBD2*01 MNH…EY SMN…VEV CASS PTGGPLT YEQYEF 1 2.4 MSC3 TRAV14/DV4*01 TRAJ49*01 TSDQ…SYG QGSY…DEQN CAMRE GYL NTGNQFYF TRBV24-1*01 1 3.2 MSC4 TRAV26-2*01 TRAJ45*01 TISG…TDY GLT…SN CILRD GFLM YSGGGADGLTF TRBV3-1*01 TRBJ2-1*01 TRBD1*01 KGH…DR SFD…VKD CATSD RTG YNEQFF 6 19.4 MSC4 TRAV26-2*01 TRAJ45*01 TISG…TDY GLT…SN CILRD GWGM YSGGGADGLTF TRBV20-1*01 TRBJ2-3*01 TRBD1*01 LGH…DT YNN…KEL CASS PRDRIQG TDTQYF 2 6.5 MSC4 TRAV41*01 TRAJ45*01 VGI…SA LSS…GK CAV T SGGGADGLTF TRBV4-1*01 TRBJ2-1*01 TRBD2*01 DFQ…ATT SNEG…SKA CSAR LAAD SYNEQFF 4 12.9 MSC4 TRAV26-2*01 TRAJ40*01 TISG…TDY GLT…SN CILRD GWG GTYKYIF - TRBJ1-1*01 TRBD1*01 MGH…RA YSY…EKL CASS PQPWGNAY TEAFF 8 25.8 MSC4 TRAV14/DV4*01 TRAJ27*01 TSDQ…SYG QGSY…DEQN CAMR NTNAGKSTF - 1 3.2 MSC4 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILR APFR FGNEKLTF - 1 3.2 MSC4 TRAV26-2*01 TRAJ48*01 TISG…TDY GLT…SN CILRD G FGNEKLTF - 8 25.8 Single-cell index-sorting analysis of TCR gene expression revealed that the subpopulations co-staining with both CD1d-endo and CD1d-α-GalCer tetramers mainly comprised TRAV26 + TCRs, indicated by red dots in the two representative donors (Fig. 2 c). These cells were also CD4 + (M = 100%) in 5 out of 6 donors analysed over 5 different index-sorting experiments, while in one donor, they were CD4 − CD8 − DN or CD4 − CD8 low (Fig. 2 c). In summary, the human CD1d-endo-reactive population harbours a public type II NKT repertoire characterised by biased TRAV26 + TCR usage and a semi-conserved CDR3a motif, often expressed as a canonical TRAV26-2-TRAJ48 rearrangement. TRAV26 + TCRs directly recognise CD1d. To test the specificity of the CD1d-endo-reactive TCRs, five paired TCRs that included three TRAV26 + clones (“T26A”, TRAV26-2-TRAJ40 TRBV19 , “T26B” TRAV26-2-TRAJ42 TRBV13-1 and “iT26”, TRAV26-2-TRAJ48 TRBV6-2 ), and two TRAV26 − clones (an αβ TCR identified in 7 , “T14”, TRAV14-TRAJ34 TRBV19 , and a γδ TCR “VD3G8”, TRDV3-TRDJ2 TRG8 ) (Tables 1 and 2 ) were transiently transfected into HEK293T cells, or transduced β2m-deficient SKW3 cells (SKW3.β2m −/− ). These two TCR transduced cell systems were assessed for binding CD1d-α-GalCer and CD1d-endo tetramers, in comparison to a control cell line expressing a type I NKT TCR “NKT15” 35 , or non-NKT controls including the T29_E 7 and the CD1c-reactive clone 3C4 32 (Fig. 2 d). The five lines stained strongly with CD1d-endo tetramers, with MFIs > 45000 in HEK293T or > 1000 in SKW3.β2m −/− cells (Fig. 2 d), unlike the negative controls. While CD1d-α-GalCer tetramers showed much lower staining of the TRAV26– lines (typically 10-100-fold less than CD1d-endo), they stained all three TRAV26 + lines to a similar degree as CD1d-endo tetramers (Fig. 2 d), reflecting the co-staining profile observed after in vitro expansion of the parental clones (Fig. 2 c). This suggested that the TRAV26 − TCRs may detect an undefined mammalian endogenous lipid presented by CD1d, and that a-GalCer can displace this lipid thereby preventing recognition, whereas the TRAV26 + lines are indifferent to the presence of a-GalCer. As expected, the type I NKT15 TCR line stained far more strongly with CD1d-α-GalCer tetramers (Fig. 2 d), whereas the CD1d-restricted lines were not stained by SAV-PE alone, nor by CD1c-tetramers conjugated to PE (Fig. 2 d), which instead specifically stained the 3C4 control. To measure TCR-mediated activation following CD1d binding, NKT TCR-transduced cell lines were co-cultured with Ag-presenting cells with differing levels of CD1d. These included: wildtype C1R cells (C1R.WT) with low CD1d expression, CD1d transductants (C1R.CD1d) with high CD1d expression, or β2m knockout C1R cells (C1R.β2m −/− ) that lack surface CD1d 7 . The TCR-transduced lines derived from CD1d-endo sorted cells upregulated the activation marker CD69 when co-cultured with C1R.CD1d, whereas C1R.WT or C1R C1R.β2m −/− cells did not cause activation (Fig. 2 e). α-GalCer elicited strong responses by the NKT15 cell line using C1R.WT or C1R.CD1d, whereas similar activation was observed in the presence or absence of α-GalCer for TRAV26 − or TRAV26 + lines (Fig. 2 e). Notably, α-GalCer did not block activation of the TRAV26 − lines despite blocking CD1d tetramer staining of these lines (Fig. 2 d), suggesting that a-GalCer was unable to saturate all CD1d molecules on the C1R Ag-presenting cells in these co-culture conditions. Thus, the newly identified TCRs confer signalling in response to CD1d, regardless of whether α-GalCer is present. Taken together, these data suggest that TRAV26 + NKT cells bind CD1d in a lipid-independent manner and represent a distinct population of human type II NKT cells. Trapping lipids between CD1d and TCRs. Two hypotheses regarding the role of lipids in CD1d-TCR binding were investigated. The first was that TRAV26 + TCRs bind CD1d in a lipid-independent fashion, reminiscent of what has been reported for CD1a 36 , 37 and CD1c 38 . The second, supported by studies of known type II NKT cell ligands, sulfatides 39 and membrane phospholipids 40 , was that some as yet unknown but ubiquitous self-lipid can increase the TCR binding-affinity to CD1d and that a-GalCer can substitute for this lipid. To test these hypotheses, the ‘TCR trap’ method 41 , 42 was employed whereby the soluble TCRs were allowed to form a complex with CD1d-endo that was subsequently purified using size exclusion chromatography, where TCR-bound CD1d molecules can be separated from non-bound CD1d molecules (Fig. 3 a). The eluents of CD1d-TCR were then compared to CD1d alone by mass spectrometry analysis to identify the lipids specifically associated with CD1d-TCR binding. The human CD1d-endo carries a heterogenous cargo of self-lipids that are detectable by nano-electrospray and reversed phase high performance liquid chromatography-mass spectrometry (Fig. 3 a) 41 , 42 . Nano-electrospray analysis was conducted on lipids that were eluted from the TCR alone, CD1d alone and CD1d in complex with the two TRAV26 + αβ TCRs (T26A and T26B), the γδ TCR (VD3G8) and the TRAV26 − αβ TCR (T14) (Fig. 3 b). For TCR alone no clear signals for lipid binding were observed, as expected (Fig. 3 a). In contrast, for CD1d alone, there were many m/z signals in negative mode. Similar to recent results with CD1a 37 , and other CD1 molecules 30 the strongest signals matched the absolute mass and alkane series patterns for sphingomyelins (SM, m/z 737.6, 765.6, 819.6, 845.6 and 847.6) and some weak signals matched for phosphatidylcholine (PC, m/z 794.6, 904.7, 906.7, 932.7 and 934.7), which are the two most abundant cellular sphingolipid and phospholipid classes, respectively. In contrast to results from a type I NKT TCR-trap study in which the TCR strongly influenced the lipids bound to CD1d 42 , CD1d in complex with T26A, T26B, VD3G8 and T14 showed a lipid pattern that was highly similar to CD1d alone. Using HPLC-MS as a more quantitative method that separates individual molecules for detection in very narrow mass windows, once again the distinct nature of each TCR in the four types of CD1d-TCR complexes, did not substantially affect the repertoire of lipids that mediated its binding to CD1d 42 . Indeed, in all cases, the patterns of lipids in CD1d-TCR complexes matched the patterns of lipids seen for CD1d endo alone (Figs. 3 a and 3 b), maintaining high SM to PC ratio 30 . Thus, no particular exogenous lipid was required for CD1d-TRAV26 + TCR complex formation, supportive of the first hypothesis that these TCRs bind in Ag-independent manner. To independently assess reactivity towards individual lipid species that include known CD1d-presented Ags that might be under-represented or absent from the mixed cargo of endogenous lipids, (dominated by SMs and PCs that were incorporated into CD1d during its biosynthesis in GnTI −/− HEK293S cells 30 , Fig. 3 a–b), we generated a panel of CD1d tetramers by exogenously loading secreted CD1d with one of the following CD1d-Ags or controls: phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), sphingomyelin (SM C34:1 or C42:2), sulfatide, lyso-(L)PE, LPC, phosphatidylglycerol (PG), ganglioside GD3, α-GalCer, 3-chlorophenyl-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonate (ClPPBF) 7 or vehicle (tyloxapol) (Fig. 3 c). Each tetramer was tested for staining the type II NKT TCR reporter lines (VD3G8, T14, T26A, T26B) and the control NKT lines that expressed the type I NKT15 TCR and the ClPPBF-reactive type II VD1G9 TCR 7 (Fig. 3 c). NKT15 and VD1G9 stained only with tetramers carrying their known cognate Ags and not with CD1d-endo. In contrast, amongst all type II NKT lines that were stained with CD1d-endo tetramers (Fig. 2 d), T26A and T26B bound CD1d tetramers at similar intensities, regardless of the ligand exogenously added (Fig. 3 c ) , including the bulky GD3 glycolipid 43 , whereas T14 and VD3G8 stained less with CD1d-α-GalCer tetramers (Fig. 3 c), and in line with Fig. 2 d. Thus, in contrast to other NKT lines tested, lipid replacement within CD1d did not markedly affect CD1d-TRAV26 TCR interactions in these systems. CD1d binding affinity of type II NKT TCRs. Using surface plasmon resonance (SPR), the affinity of the interaction between three soluble type II NKT TCRs towards CD1d-endo and CD1d bearing sulfatide, GD3 or α-GalCer was examined. The T26A TCR bound to CD1d-endo with an affinity of ~ 7.8 µM and this was not impacted by the type of lipid associated with CD1d, with K D values ranging from 7.8 µM to 10.6 µM (Fig. 4 ). Similarly, the T26B TCR bound to CD1d-endo or CD1d with each of the three defined lipids with a similar range of affinities (5.8–15.6 µM) (Fig. 4 ). Conversely, the T14 TCR exhibited a finer specificity to the lipids presented by CD1d (Fig. 4 ). Here, whilst the T14 TCR bound to CD1d-endo, CD1d-sulfatide and CD1d-GD3 with K D values of 13.5, 20.4 and 41.1 µM, respectively, it did not bind to CD1d-⍺-GalCer ( K D >200 µM), in agreement with the lack of CD1d-⍺-GalCer tetramer staining of this line (Fig. 2 d ) . Furthermore, none of the tested ligands, including sulfatide, GD3, SM or ⍺-GalCer, enhanced activation of the type II NKT TCR-transduced cell lines measured by CD69 upregulation, whereas ⍺-GalCer elicited stronger activation of the NKT15 type I NKT TCR line, over that elicited by C1R.CD1d or C1R.WT cells ( Fig. S3a ). These responses reflected specific NKT TCR-CD1d interactions, as they were blocked by anti-CD1d, whereas the control AF7 MAIT TCR 44 , 45 expressing cells only activated in the presence of 5-OP-RU ( Fig. S3b ). Collectively, these results suggest that the TRAV26 + TCRs interact with CD1d with similar affinity irrespective of the lipid bound. Structure of the TRAV26 + type II NKT TCR-CD1d-lipid complex. We determined the crystal structure of the T26A NKT TCR-CD1d-endo ternary complex (Fig. 5 a and Table S1 ). The T26A NKT TCR docked ~ 100° across the main axis of the CD1d Ag-binding cleft, being positioned over the 'left' side of the platform on the A'-roof of CD1d, sitting closer to the ⍺ 2 -helix (Fig. 5 a). This docking position clearly contrasted to type I NKT TCR-CD1d-lipid binding (Fig. 5 d). This 'left-shifted' binding footprint was more reminiscent of the recognition strategy adopted by CD1a autoreactive TCRs 3 , 41 , CD1d-sulfatide-reactive type II NKT TCRs 19 , 20 (Fig. 5 c) and some ‘atypical’ human NKT TCRs 22 , 23 , 24 , 25 , 26 whereby the TCRs contacted CD1d and the lipid presented. Mass spectrometry analysis of the T26A TCR-CD1d-endo demonstrated that although mixed lipids were bound, long chain SM (> C40) appeared to be the major species present (Fig. 3 a ). In line with this, we modelled and refined SM (C40:2) as the bound endogenous lipid into the unbiased electron density that was clearly visible within the CD1 cleft (Fig. 6 a & Fig. S2 a ). The T26A TCR did not directly contact the protruding headgroup of the lipid bound within the CD1d cleft whereby the most proximal residue to SM was located > 7Å away (Fig. 6 b ) . This distal mode of binding can explain why these TCRs seemingly bind to CD1d in a lipid-independent manner and indeed tolerate binding to CD1d carrying lipids with head groups that differ in size and shape (Figs. 3 and 4 ). Thus, the TRAV26A + NKT TCR contacts CD1d itself, which breaks the CD1d-lipid co-recognition paradigm. Structural basis of TCRa chain bias towards CD1d. Upon complexation, the buried surface area (BSA) of the T26A NKT TCR-CD1d-endo complex (~ 600 Å 2 ), fell outside the range for type I NKT TCR-CD1d ternary complexes (760–860 Å 2 ) and was significantly lower than the mouse type II NKT TCR-CD1d-lipid complexes (~ 1000 Å 2 ) 19 , 20 , 21 . The TCRα and TCRβ chains of T26A contributed ~ 75% and ~ 25% of the total BSA at the TCR-CD1d interface, respectively, with both the CDR1α (21% BSA) and CDR2α (16% BSA) loops contributing to the TCR-CD1d interface thereby providing immediate insight into the TRAV26 bias. Conversely, the CDR1β and CDR2β did not interact with the CD1d-endo complex, explaining the broader observation of TRBV gene diversity amongst TRAV26 TCRs (Table 1 ). The CDR1α loop sat peripherally above the α2-helix of CD1d whereby Thr30α interacted with Trp160, Gly164, Thr165 and Gln168 residues of CD1d, while Tyr32α stacked against Glu156 and Trp160 (Fig. 6 c and Table S2 ). Ser28α contacted only Gln168 while Gly29α contacted Gly164 and Gln168 of CD1d via van der Waals (VDW) and hydrogen bond interactions, respectively (Fig. 6 c and Table S2 ). Within the CDR2α loop, Leu51α, Thr52α and Ser53α contacted Asn163 of CD1d and its N-linked glycans (N-acetylglucosamine, NAG) (Fig. 6 c and Table S2 ). Further, the germline encoded framework His49α that precedes the CDR2α loop established a VDW interaction with Glu156 in CD1d ( Table S2 ). Interestingly, Thr30α, Thr52α and Ser53α mediated several contact points with CD1d and were not conserved in TRAV26-1 genes, providing molecular insight for why TRAV26-2 may be over-represented between the two genes amongst CD1d-endo-reactive cells (Table 1 ). The CDR3α and CDR3β loops dominated the interactions at the interface with 35% and 25% BSA, respectively (Fig. 6 d). The CDR3α and CDR3β loops were positioned more centrally over the CD1d binding-cleft. Here, Arg99β from the CDR3β loop plunged into the CD1d-binding cleft to form VDW interactions with Trp153, Thr157 and Trp160, while Pro100β contacted Glu156 of CD1d (Fig. 6 b). The non-germline encoded Gly-Trp motif, which is conserved in 6 out of the 39 TRAV26-2 clones from 4 distinct donors (Fig. 2 b and Table 2 ), established multiple contacts with CD1d (Fig. 6 d). Whereas in 18 of the 39 TRAV26-2 clones, a Phe residue was present at this position, which constitutes a Gly-Phe motif (Fig. 2 b and Table 2 ). Interestingly, this Phe residue was germline-encoded in 7 of the TRAV26-2-TRAJ48 + clones across 6 donors. The other 11 clones harbouring the Gly-Phe motif were all non-germline encoded (Fig. 2 b and Table 2 ). Conservation of bulky aromatic residues within the CDR3α across 74% of the TRAV26-2 + clones may be a key structural determinant governing the TCR docking topology. Further, bias towards Phe may also explain the relatively high occurrence of TRAV26-2–TRAJ48 rearrangements. The G93⍺ residue was also highly prevalent in both motifs, which might be preferentially selected over other larger amino acids to avoid steric clashes with Trp160 and/or CDR3β residues (Fig. 6 d). This finding aligned with the additional patterns observed for TRAV26-2 isolated sequences in positions 6 and 7 (Fig. 2 b bottom ) and emphasized the need for a bulky residue in position 7. Collectively, these results suggested that the germline residues encoded by the TRAV26-2 gene, and the rearrangement of non-germline-encoded structural motifs to Gly-Phe/Trp, played a key role in determining the docking modality adopted by the T26A TCR over the α2-helix A′-roof of CD1d. A common mode of recognition of self-lipids by the T26A NKT TCR. Structural studies on the T26A TCR-CD1d-lipid recognition were extended by loading GD3 into CD1d ( Fig. S2 b) and determining the crystal structure of the ternary complex (Fig. 5 ). The electron density for the bound GD3 was partially visible whereby only the first glucose moiety of the headgroup and both lipid tails could be modelled (Fig. 6 e and Fig. S2 c ). The crystal structure revealed a nearly identical docking mode to that of CD1d-endo complex that was modelled as CD1d-SM (Fig. 5 ). The majority of the molecular interactions at the T26A NKT TCR-CD1d-GD3 interface were also conserved ( Fig. S2 d-e and Table S3 ). Indeed, the T26A NKT TCR did not contact the GD3 lipid, as the most proximal TCR residue, Arg99β from the CDR3β, was 10Å away from the glucose moiety (Fig. 6 f). Other sphingolipid Ags such as α-GalCer would be expected to produce similar observations ( Fig. S2 f ). Collectively, our structural analysis of the T26A type II NKT TCR suggests a new molecular paradigm for CD1d recognition whereby the type II TRAV26 + NKT TCR can bind CD1d in a lipid-independent manner. Molecular footprint of TRAV26 type II NKT TCRs onto CD1d. Having established that lipid Ags had little impact on TRAV26 + TCRs binding to CD1d, the next step was to assess their functional CD1d docking footprints. Here, C1R cell lines overexpressing wild type CD1d or alanine-substituted CD1d mutants targeting solvent-exposed residues of CD1d 7 were used to test their ability to stimulate the TRAV26 + and TRAV26 − TCR-transduced cell lines (Fig. 7 ). CD69 upregulation on the NKT15 TCR control line was inhibited by the alanine mutations of Glu83, Val147, Lys86, and Met87, all positioned near to the F'-portal of CD1d, consistent with our previous results 7 and the ‘right-shifted’ parallel docking strategy adopted by type I NKT TCR(s) 35 (Fig. 7 ). In contrast, the three TRAV26 + TCR transduced cell lines were not impacted by those mutations but were inhibited (> 75%) by mutations of two CD1d residues Gln62 and Trp160, located distant from the F′-portal, where Ags protrude. These data complement the structural data showing that TRAV26 + TCRs bind the A′-roof. The impact of the CD1d alanine mutant scan was similar, but not identical, across the three TRAV26 TCR lines. This outcome likely reflects differences in CDR3α and TCRβ chain pairing, and their influence on CD1d-binding. Activation of both TRAV26 − TCR transduced lines (T14 and VD3G8) was severely impacted by mutations of Trp160 and His68, which sit in the A'-roof of CD1d, in addition to other residues closer to the Ag portal, spanning to the F'-roof. Specifically, T14 was moderately inhibited by mutations of Val72, Thr157, Glu83 and Val147 and VD3G8 impacted by Thr157, Glu83, whereas Arg79Ala mutation led to enhanced activation, suggesting that Arg79 interferes with optimal VD3G8 TCR binding to CD1d. Thus, these TRAV26 − TCRs appeared to dock more centrally and over the Ag portal, which likely reflects their differences in sensing CD1d-bound ligands (Figs. 2 c, 3 c and 4 ), unlike the extreme A'-roof CD1d-docking by TRAV26 + TCRs. Collectively, these data suggest that TRAV26 + NKT TCRs bind to CD1d in a left-shifted approach and ligand-independent manner. DISCUSSION Currently, the CD1d-restricted repertoire is thought to comprise a highly conserved population of type I NKT cells, and a group of diverse type II NKT cells. Here, we identify a public population of type II NKT cells defined by a TRAV26 TCR bias and a conserved CDR3a motif and we provide detailed molecular insight into their mode of lipid-independent CD1d recognition. With wider implementation of CD1 tetramers to systematically investigate TCR repertoires, we are increasingly detecting conserved patterns and public TCR usage for particular CD1-Ag pairs 7 , 46 , 47, 48, 49 . A general view emerging from these studies is that NKT cells are not exclusively represented by a public TCR, but instead that non-polymorphic CD1 proteins generate an underlying network of T cells shared across donors, with many conserved families of TCRs and Ags. The epitope for the TRAV26 TCR is CD1d itself rather than a defined lipid. Thus, an exposed A'-roof is likely a common or nearly universal epitope in humans, which could account for the several distinct TRAV26-TRAJ48 + T cell clones seen in every donor tested here. These data connect to a prior study where two distinct TRAV26-2 encoded TCRs ( TRAV26-2—TRAJ48 and TRAV26-2—TRAJ44 ) were reported among 14 TRAV10 − TRAJ18 − TRBV25 − TCRs isolated with CD1d-a-GalCer tetramers 25 , albeit not recognised as a conserved motif through the strategy employed at the time. The Ag-independent mode of CD1d recognition by germline-encoded TRAV26 TCR residues and a conserved CDR3α motif raises interesting questions about the evolutionary pressures that lead to the conservation of TCRs to act as pattern recognition receptors against CD1d. Thus, our results also suggest that some type II NKT cells might be poised to sense overall changes in surface expression of the Ag-presenting molecule CD1d, rather than the lipid-Ag itself. Accordingly, changes in surface expression levels of CD1d have been shown to impact NKT cell function 50 and are often associated with infection 51 , 52 , 53 , 54 , cancer 55 and autoimmunity 56 . For example, hepatocytes that are chronically infected with Hepatitis C display high CD1d surface expression relative to healthy tissue or other liver disease, to levels that resemble those of C1R.CD1d transfectants published within the same study to elicit IFN-γ release from intrahepatic CD1d-reactive T cells (Type II NKT) 57 . Similarly, another study demonstrated that CD1d overexpression can be targeted by mouse CD1d-reactive Vγ4 + T cells, promoting viral myocarditis sequela of coxsackievirus infections 58 . Whether these physiological contexts can lead to activation of TRAV26 + NKT cells is an important question for further exploration. Whilst some type II NKT clones can display lipid-Ag specificity 19 , 20 , 21 , 59 , 60 and mount lipid Ag-driven responses 12 , 13 , 61 , other type II NKT cells also retain the ability to recognise CD1d carrying multiple self-Ags 4 , 27 , 28 , 59 possibly as a strategy to sense early stress signals in an innate-like fashion 55 , 62 , 63 , 64 . Self-reactive profiles have been reported amongst other CD1-restricted lipid-reactive T cells in humans 2 and ligand-independent interactions have been described for CD1a 37 , 65 , CD1b 66 , CD1c 38 and CD1d 67 , and MR1 68 , where the structural mechanism in part relies on smaller Ags hiding inside antigen-binding clefts (particularly for the CD1 system) 3 . However, non-permissive lipids, such as long chain SM (42:2), bound by CD1a or CD1c can prevent docking of endo-reactive TCRs 38 , 41 , 69 . Here, we show that TRAV26 TCRs engage CD1d when displaying a variety of headgroup-containing lipids, over the extreme side of the A´-roof, without contacting the protruding headgroups. Accordingly, both the α1 and α2helixes of the A´-roof are heavily contacted by TRAV26-2 TCR α-chain and may form an anchor region within CD1d targeted by non-type I NKT TCRs, including the ‘atypical’ CD1d-α-GalCer reactive NKT TCRs ( TRAV10–TRAJ18 − ) 22, 23, 24, 25, 26 , CD1d-benzofuran-self-lipid reactive type II NKT TCRs 7 , and the murine sulfatide reactive TCRs 19 , 20 . However, all previously structurally described CD1d interactions involve NKT TCR co-engagement of CD1d and their cognate lipid, which contrasts our novel study of TRAV26 + TCRs. Limitations of the Study and future directions The TCR patterns identified among CD1d-endo reactive clones followed in vitro expansion of sorted cells, which is commonly used in studies of rare populations 7 , 22 , 24 , 32 and was necessary for us to confidently identify these cells. While it is possible this may have altered the representation of some TCRs within the population, the expansion is based on anti-CD3 stimulation and therefore should not inherently favour any particular TCRs. While this approach precludes addressing immune-function ex vivo, nonetheless, we have shown that expanded TRAV26 cells are capable of producing a range of cytokines, in particular TNF and IFNγ, implying that these cells have pro-inflammatory potential and future studies will investigate their contributions to various health and disease states. It will also be important to address the intrinsic or extrinsic regulatory mechanisms that define the activity and immune function of TRAV26, including their reliance on secondary signals such as cytokines 64 or other receptors such as NK receptors 70 , which can play a role in modulating activation status in a TCR-independent manner. Most importantly, our findings suggest that TRAV26 cells are highly represented within the CD1d-endo reactive population and are present as a public TCR in essentially all individuals tested. The potential significance of these observations is highlighted by an earlier study where we revealed the TRAV12-TRAJ6 type II NKT TCR motif 7 , specifically reactive to small benzofuran-like molecules bound by CD1d. That TCR motif was subsequently implicated in Crohn’s disease 71 , 72 where the cells were named Crohn’s-associated invariant T cells (CAIT cells), which is now underpinning studies to investigate the contributions of CAIT cells and the CD1d axis to this disease. Several candidate therapies have explored the immunomodulating potential of type I NKT cells, with ongoing trials also including CAR-type I NKT cell allogenic and adoptive therapies 73 . The findings of this study may offer new avenues to modulate immune responses through the monomorphic protein CD1d and overcome existing limitations of current trials, that require a-GalCer co-delivery to allow type I NKT-activation 74 . Moreover, our observation that TRAV26 TCRs retain their ability to recognise the complex glycan headgroup of GD3 loaded onto CD1d, which inhibits type I NKT responses 43 , flags their potential exploration in therapies against GD3-expressing cancers. These findings further highlight the possibility of future immunomodulation agonists, antagonists or anti-TCR antibodies to selectively manipulate these public TRAV26 + type II NKT cells. METHODS Flow cytometry. Buffy coats from healthy blood donors were obtained from the Australian Red Cross Blood Service (agreement 13-04VIC-07), and all experiments were conducted in accordance with the University of Melbourne Human Research and Ethics committee guidelines (approval number 1035100). PBMCs were prepared through density gradient centrifugation using Ficoll-Paque (GE Healthcare). Cells were incubated for 10 min with Fc-receptor block (BD Pharmingen) and 5% (v/v) mouse serum, followed by CD1d-endo tetramers for 30min on ice. Where described, CD1d–endo tetramer + cells were enriched by TAME, using anti-phycoerythrin (PE) magnetic beads and LS columns (Miltenyi Biotec), and stained with secondary antibodies including: CD3ε (UCHT1, eBioscience and Becton Dickinson), CD4 (RPA-T4, BD Pharmingen), CD8α (SK1, BD Pharmingen), CD19 (HIB19, BioLegend), CD14 (MφP9, BD Pharmingen), TCRγδ (11F2, BD Pharmingen), and 7-aminoactinomycin D (7AAD) viability dye (Sigma). CD3 + CD1d–endo tetramer + cells were sorted using a FACSAria (BD Biosciences). When reassessed immediately after the first-sort, purities ranged 13–65%. Where described, sorted cells were then expanded for 18–21 days, whereby in the first two they were exposed to plate bound anti-CD3 (10 µg/mL, UCHT1, BD Pharmingen) and anti-CD28 (5µg/mL, CD28.2, BD Pharmingen), in the presence of IL-2 (20 U/mL, Prepotech) IL-7 (50 ng/mL, eBioscience) and IL-15 (40 pg/mL), in complete RPMI-1640 supplemented with 10% (v/v) FBS (JRH Biosciences), penicillin (100 U/ml, Sigma), streptomycin (100 µg/ml), Glutamax (2 mM), sodium pyruvate (1 mM), nonessential amino acids (0.1 mM), HEPES buffer (15 mM, pH 7.2–7.5) (all from Invitrogen, Life Technologies) and 2-mercaptoethanol (50 µM, Sigma). After expansion cells were re-stained with CD1d-endo tetramers alone, followed by surface antibodies and secondary CD1d-endo as well as CD1d-α-GalCer tetramer staining. These sorted and expanded CD3 + CD1d-endo tetramer + cells were then index-sorted as single cells for TCR sequencing. Data analysis was completed using FlowJo (Tree Star Inc), and graphs generated using GraphPad Prism. Lipids. α-GalCer C24:1 (PBS44) used for CD1d tetramers was kindly provided by P. Savage (Brigham Young University). α-GalCer C26:0 used for cellular activation assays was supplied by Alexis Biochemicals, and SM C42:2, SM C34:1, PC C42:1; sulfatide C42:2, PE C36:1, PS C36:1 PC C36:1, PC C42:2, PI C36:1, PG C36:1, LPE C18:1, LPC C18:1, pLPE C18:1 from Avanti Polar Lipids. Disialo-ganglioside GD3 C34:1 was purchased from Matreya. CD1d-ligands were dissolved in tris buffer saline (TBS) alone (pH 8) or TBS containing 0.05% v/v tyloxapol (Sigma), or buffer containing 0.5% v/v tween-20, 57 mg/ml sucrose and 7.5 mg/ml histidine, and exogenously loaded overnight into soluble biotinylated CD1d at 12-fold molar excess (except for α-GalCer - loaded at 6-fold), prior to tetramerization. Identification of the NKT TCRs. CD3 + CD1d-endo tetramer + cells were single-cell sorted from CD1d-endo tetramer-enriched and culture-expanded NKT cells (as described above), and cDNA generated using 0.1% Triton X-100 (Invitrogen) and SuperScript VILO according to manufacturer’s instructions. Paired TCRα and TCRβ or TCRγ and TCRδ chain-transcripts were amplified as previously described 31 . PCR products were sequenced at the AGRF facility (Australia) and analysed using IMGT 75 . TCR nomenclature is presented in accordance with the IMGT guidelines. Unproductive TCR gene rearrangements were excluded from analysis. The first 10 amino acids of the CDR3α of TRAV26 TCRs shown in Fig. 2 b were aligned using Logomaker 76 . Generation of stable cell lines and stimulation assay. TCR constructs containing the full-length TCRα and TCRβ or TCRδ and TCRγ chains separated by a 2A-cleavable linker were synthesized (Genscript) and cloned into the pMIGII plasmid. TCR-deficient SKW3.β2m −/− cells were retrovirally transduced with the TCR and a 2A-cleavable human CD3 77 , plus the packaging vectors pEQ-Pam-3-E pVSV-G and using HEK293T cells as packaging cells and FUGENE 6 (Promega), as previously described 78 . The pMIGII, expression and packaging vectors were provided by Dr. Dario Vignali (St. Jude’s Research Hospital, USA), and the CD3 expression vector was provided by Prof. Stephen Turner (Monash University, Australia). CD3(GFP) hi cells were sorted and assessed for their ability to bind CD1d tetramers by flow cytometry. For Fig. 2 C, HEK293T cells were transiently transduced with CD3 and TCR vectors in the same manner but in the absence of packaging vectors and assessed after 48h for CD3/TCR expression and CD1d-tetramer binding by flow cytometry. C1R cells were transduced to express human CD1d or mutated versions of CD1d, akin to SKW3.β2m −/− cells, and purified using flow cytometric sorting to produce stable cells lines expressing similar surface levels of CD1d 7 . Activation assays. For stimulation assays, TCR-expressing SKW3.β2m −/− cells were co-cultured overnight in complete RPMI (as described above), with or without C1R cells (either C1R.WT, C1R.CD1d or C1R.β2m −/− ) cells, with α-GalCer C26:0 at 1 µg/mL, sulfatide C42:2, SM C42:2 or GD3 C34:1 at 20 µg/mL, or vehicle controls, and with either anti-CD1d (51.1, Biolegend), isotype control antibody (MPC-11 or MG2b-57, Biolegend) or media alone, in round-bottom 96-well plates. Activation of TCR-transduced cells was analysed by flow cytometry for CD69 upregulation using anti-CD69 (FN50, BD Pharmingen). For functional analysis of PBMCs, CD1d-endo tetramer positive or negative cells that had been FACS-sort expanded for 20 days as described above were exposed to 10 ng/mL PMA, 1 µg/mL Ionomicyn and 1/1000, Golgi stop (1/500, BD Pharmingen), Brefeldin A (1/1000, BD Pharmingen) and for 4h in complete media prior to assessment of intracellular cytokine production using BD Cytofix/Cytoperm kit (BD Biosciences), anti-TNF (MAb11, BD Pharmingen), anti-IFNg (4S.B3, Biolegend) and anti-IL-13 (JES10-5A2, BD Pharmingen). CD1d and NKT TCRs production and purification. The human CD1d sequence encoding for truncated recombinant human CD1d ectodomain harbouring a C-terminal BirA and six-histidine (GSGLNDIFEAQKIEWHEHHHHHH) affinity tags, and β2-microglobulin, both in separate pHLsec vectors, were co-transfected into GnTI −/− HEK293S for expression using polyethyleneimine as described 7 , 79 . The soluble CD1d glycoprotein was purified by Ni/NTA affinity purification followed by size-exclusion chromatography using a Superdex 200 16/60 column (GE Healthcare). CD1d was enzymatically biotinylated using biotin ligase (produced in-house) and further purified by size-exclusion chromatography using a Superdex-75 16/60 gel-filtration column (GE healthcare), followed by storage at − 80°C. Biotinylated CD1d proteins carrying endogenous lipids (endo), or exogenously loaded in vitro (as described in the lipids section) were tetramerised using SAV-PE or SVA-BV421 (Biolegend). The genes encoding the T26A (TRAV26-TRBV19), T14 (TRAV14-TRBV19) and T26B (TRAV26-TRBV13) TCRs after codon optimization, were synthesized (Genscript) and cloned into the expression vector pET30 (Novagen). The TCRα and TCRβ chains of the three NKT TCRs were expressed in Escherichia coli strain BL21 and purified as inclusion bodies (IBs) as described 17 . The IBs were resuspended in the following buffer: 8 M urea, 0 mM Tris-HCl-pH 8.0, 0.5 mM Na-EDTA, 1 mM DTT. The three TCRs were refolded by dilution in a solution containing 5 M urea, 0.1 M Tris-HCl-pH 8.0, 2 mM Na-EDTA, 400 mM L-arginine-HCl, 0.5 mM oxidized glutathione, 5 mM reduced glutathione. The refolding solutions were then dialyzed against 10mM Tris pH 8.0. The NKT TCRs were purified by Diethyl aminoethyl (DEAE) anion exchange, size exclusion and HiTrap-Q anion-exchange chromatography techniques. In vitro loading of lipids into human CD1d for crystallography and SPR. Lipid solutions of GD3, sulfatide and ⍺-GalCer were prepared at 1 mg/mL in 0.5% tyloxapol. Prior to lipid loading, the lipid solutions were sonicated for 30 mins and immediately transferred to a 60°C water bath for 1 min and left to cool at room temperature for 1 min. The lipids GD3,sulfatide were then added directly to CD1d-endo at a 3–6:1 molar ratio and incubated in 10ml TBS150 (Tris buffered saline, 150mM NaCl, 10mM Tris pH 8.0) at room temperature for 15 h. The lipid-loaded CD1d were then purified by MonoQ anion-exchange chromatography (GE Healthcare). α-GalCer was loaded at a 6:1 molar ratio into the purified CD1d-GD3 binary complex and purified by MonoQ anion-exchange chromatography. Purification of TCR-CD1d-endo complex and mass spectrometry analysis. The T26A, T26B or T14 TCRs were incubated with CD1d-endo for 16 hours. The mixture was then subjected to gel filtration on a Superdex 200 16/60 column (GE Healthcare) to isolate the TCR-CD1d-endo ternary complex. The ‘TCR trap’ assay was performed as previously described with minor changes 41 , 42 . The gel filtration protein fractions were subjected to Bligh and Dyer extraction, and the extracted lipids were initially analysed by shotgun nano-electrospray on a Thermo Fisher LXQ Ion Trap mass spectrometer. For the semi-quantitative, high resolution mass analysis, the lipid eluents were normalized to 20 µM based on the input proteins and 10 µl was injected into a reversed-phase HPLC system (Agilent Poroshell EC-C18 column, 1.9-micron, 3 x 50 mm) with an Agilent 6520 Accurate-Mass Q-TOF mass spectrometer. The gradient conditions were modified from a prior method (Klooster, elife, 2020): the mobile phases were (A) 2 mM ammonium formate in 90/10 methanol/water (v:v) and (B) 2 mM ammonium formate in 90/10/0.1 1-propanol/cyclohexane/water (v:v:v). The 30-minute gradients were: 0–4 min of 100% A, 4–13 min from 100% A to 100% B, 13–18 min of 100% B, 18–20 min from 100% B to 100% A, and 20–30 min of 100% A. Surface plasmon resonance (SPR) measurements and analysis. All the experiments were performed at 25°C on Biacore 3000 and T200 using HBS buffer (10 mM HEPES- HCl - pH 7.4, 150 mM NaCl). Biotinylated CD1d-endo, CD1d-sulfatide, CD1d-α-GalCer and CD1d-GD3 were coupled (~ 3,000 RU) onto a research-grade SA chip and the four TCRs were applied at a flow rate of 5 µl/min. The first flow cell was left blank and was used as a reference for subsequent analysis. The final response was calculated by subtraction of the response of the streptavidin-coated chip alone from that of TCR-CD1d-lipid interaction. BIAevaluation Version 3.1 (Biacore AB) and Biacore T200 Evaluation Software 3.2.1 were used to fit the data to the 1:1 Langmuir binding model. GraphPad Prism 10 was used for data presentation. Crystallization, structure determination and refinement. The T26A NKT TCR-CD1d-endo (7 mg/ml) and the T26A NKT TCR-CD1d-GD3 (7 mg/ml) ternary complexes were both crystallized in 16–24% PEG 3350, 0.1M sodium citrate, 0.1 M citrate-bis-Tris-pH 7 using the hanging-drop diffusion method at 20°C. The crystals were cryoprotected in 10% glycerol and flash-frozen in liquid nitrogen. Crystallographic data were collected at the MX2 beamline (Australian Synchrotron). Data were processed with the XDS software 80 and scaled using SCALA from the CCP4 suite of programs 81 . The crystal structure of the T26A NKT TCR-CD1d-endo ternary complex was determined by molecular replacement method using PHASER 82 and the TCRα (Protein Data Bank accession code: 6RSY) 83 , TCRβ (PDB accession code: 5JHD) 84 and human CD1d–α-GalCer (PDB accession code: 2PO6) 35 as search models. The crystal structure of the T26A NKT TCR-CD1d-GD3 ternary complex was also solved by molecular replacement using PHASER and the T26A NKT TCR-CD1d-endo ternary complex as a search model. Both ternary complexes were refined using the Phenix refinement program 85 , and the COOT program 86 was used for macromolecular model building. The quality of the structures was validated using the Research Collaboratory for Structural Bioinformatics Protein Data Bank Data Validation and Deposition Services. All structural diagrams were created using PyMOL 87 . Declarations Data Availability The coordinates of the T26A NKT TCR-CD1d-SM and T26A NKT TCR-CD1d-GD3 ternary complexes were deposited in the Protein Data Bank (PDB) database under the accession codes 8SGB and 8SGM, respectively. All remaining data are available within the article and associated files and upon reasonable request from the corresponding authors. Source data are provided in this paper. Acknowledgments We are grateful to Paul Savage (Brigham Young University, UT, USA) and Spencer Williams (Bio21, University of Melbourne, Australia) for providing lipid antigens, and Dr Sidonia Eckle for providing the MAIT TCR control SKW3 line (clone AF7). We thank staff from the Flow Cytometry facility at the Peter Doherty Institute, David Price (statistician at the Doherty Institute) for advice on data distribution display and staff at the MX2 beamline at the Australian Synchrotron and Macromolecular Crystallization Platform 88 . This work was supported by a University of Melbourne Early Career Researcher grant (C. F. A.), the National Health and Medical Research Council of Australia (NHMRC: 1145373, 1113293, 200891, 31106741, 2008913 and 2029256), the Australian Research Council (ARC: DP170104386, DP210103064 and DP220102402). D. G. P. was supported by a CSL Centenary Fellowship and is now supported by a Sylvia & Charles Viertel Fellowship; D. I. G. was supported by an NHMRC Senior Principal Research Fellowship (1117766) and subsequently, an NHMRC Investigator Award (2008913). J. R. is supported by an NMHRC Investigator Award (2008981). D. B. M. is supported by the NIH (AR 048632, AI 049313). D.B.M and J.R. are supported by a Welcome Trust Discovery Award. Author contributions K. C. Y. P. and C. M. H. are joint co-first authors who along with, T. Y. C., R. L., E. B., C. V. N-R., C. S., S. J. J. R, C. M., A.P.U. and C. F. A. contributed to data generation, data analysis and/or paper editing. D. B. M., J. R., D. I. G, D. G. P., J. L. N. and C. F. A. contributed to project conceptualisation, funding acquisition, data interpretation, paper reviewing and editing. K. C. Y. P. and C. M. H., J. L. N. and C. F. A. co-wrote the initial draft. Conflicts of interest D. I. G and C. F. A hold two patents on CD1-targetting for immune modulation. References Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ (2004) Van Kaer, L. 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Acta Crystallogr D 66:486–501 Pymol The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC Aragao D et al (2018) MX2: a high-flux undulator microfocus beamline serving both the chemical and macromolecular crystallography communities at the Australian Synchrotron. J Synchrotron Radiat 25:885–891 Additional Declarations Yes there is potential Competing Interest. D. I. G and C. F. A hold two patents on CD1-targetting for immune modulation. Supplementary Files PoaandHarpurSupplementaryinformation.pdf Supplemental material Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7004764","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":552248410,"identity":"002a3dee-ec16-492b-bced-c166b473dd39","order_by":0,"name":"Kean CY Poa","email":"","orcid":"","institution":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, 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1","display":"","copyAsset":false,"role":"figure","size":1134475,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIdentification of CD1d-endo-reactive T cells in PBMCs. \u003c/strong\u003e(\u003cstrong\u003ea\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003eRepresentative flow cytometry plots showing pre- and post-CD1d-endo tetramer associated magnetic enrichment (TAME), gated on 7AAD\u003csup\u003e−\u003c/sup\u003eCD14\u003csup\u003e−\u003c/sup\u003eCD19\u003csup\u003e−\u003c/sup\u003eCD42b\u003csup\u003e-\u003c/sup\u003e single lymphocytes. CD1d-endo tetramer\u003csup\u003e+ \u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e cells (red gate) were sorted and expanded \u003cem\u003ein vitro\u003c/em\u003e with plate bound anti-CD3 and anti-CD28 in the presence of IL-2, IL-7 and IL-15. After 21 days, samples were reassessed for their ability to bind CD1d-endo tetramers. Violin plots depict median +/- interquartile range (IQR) of CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e within CD3\u003csup\u003e+\u003c/sup\u003e cells, and each symbol represents an individual donor (33 over 20 experiments for post-TAME, 37 over 21 experiments for 21 days post sort-expansion), coloured according to whether CD36 block was performed prior to CD1d-tetramer staining and/or CD42b\u003csup\u003e+\u003c/sup\u003e cells excluded. Stars represent donors (9 over 3 experiments) where no TAME was performed prior to sorting and expansion. After \u003cem\u003ein vitro\u003c/em\u003e expansion, both CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e (red) or CD1d-endo-tetramer\u003csup\u003e-\u003c/sup\u003e (dark grey) populations were assessed for expression of gδ TCR (\u003cstrong\u003eb,\u0026nbsp; \u003c/strong\u003e\u003cem\u003en\u003c/em\u003e=25 donors), and CD4 or CD8 within the gδ TCR\u003csup\u003e-\u003c/sup\u003e ab T cell compartment (\u003cstrong\u003ec, \u003c/strong\u003e\u003cem\u003en\u003c/em\u003e=29 donors), with data summarised in the violin plots, as per (a). (\u003cstrong\u003ed\u003c/strong\u003e) Representative overlay dot plots from 3 donors show CD3 \u003cem\u003eversus\u003c/em\u003e CD1d-endo tetramer (top) or CD1d-endo tetramer \u003cem\u003eversus\u003c/em\u003e CD1d-a-GalCer tetramer co-labelling (bottom) in cells that had expanded for 21 days after being sorted as CD1d-endo tetramer\u003csup\u003e+ \u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e (red) or CD1d-endo tetramer\u003csup\u003e- \u003c/sup\u003eCD3\u003csup\u003e+ \u003c/sup\u003e(grey underlay). Violin plot shows median +/- IQR of CD1d-a-GalCer tetramer\u003csup\u003e+\u003c/sup\u003e co-labelling of CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e expanded cells (18 donors over 14 experiments). (\u003cstrong\u003ee\u003c/strong\u003e) Overlay dot plots show TNF \u003cem\u003eversus\u003c/em\u003e IFNg or IL-13 intracellular staining on stimulated CD1d-endo tetramer \u003csup\u003e+\u003c/sup\u003e cells (in red) or CD1d-endo tetramer\u003csup\u003e –\u003c/sup\u003e (grey) sorted cells that had been expanded \u003cem\u003ein vitro\u003c/em\u003e for 21 days. Quadrant placement was based on unstimulated controls (21 days post-sort and expansion \u003cem\u003ein vitro\u003c/em\u003e). Bar graphs summarise cytokine production percentages +/- 95% confidence intervals from 6 donors across 4 experiments. The symbols in graphs shown in (\u003cstrong\u003eb-e\u003c/strong\u003e) are coded as per (\u003cstrong\u003ea\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/b5b72ca82c075222ea81778b.png"},{"id":97512942,"identity":"32c6e174-461d-4308-ac98-6a6ffa47093b","added_by":"auto","created_at":"2025-12-05 09:32:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1399471,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTCR usage amongst CD1d-endo tetramer\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e+ \u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eT cells. \u003c/strong\u003eCD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e T cells were single-cell index-sorted by flow cytometry and TCR sequences determined by nested PCR. (\u003cstrong\u003ea\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003ePie charts showing \u003cem\u003eTRAV and TRBV \u003c/em\u003egene segment diversity, and \u003cem\u003eTRAJ\u003c/em\u003e gene usage amongst TRAV26\u003csup\u003e+\u003c/sup\u003e cells derived from 14 donors over 7 experiments. (\u003cstrong\u003eb\u003c/strong\u003e) Invariant TRAV26-2-TRAJ48 rearrangement identification across different donors, and sequence conservation of the CDR3α from \u003cem\u003en=39\u003c/em\u003e TRAV26-2 clones. Hydrophobic (green) and charged (blue) residues are shown alongside the most common positions for non-germline encoded residues (grey highlight). (c) Representative overlay dot-plots of index-sorted TRAV26\u003csup\u003e+\u003c/sup\u003e\u003cem\u003e \u003c/em\u003e(red) and total T cells post-culture (grey). Violin plot summarises the CD4/CD8% distribution with median +/- interquartile-range (IQR) of TRAV26\u003csup\u003e+\u003c/sup\u003e cells index-sorted from 6 donors over 5 experiments. Five distinct TCR sequences (from \u003cstrong\u003eTable 1\u003c/strong\u003e) were used to generate transiently transfected HEK293T cells (top) or TCR-transduced SKW3.β2m\u003csup\u003e-/- \u003c/sup\u003eclones (bottom). (\u003cstrong\u003ed\u003c/strong\u003e) Representative dot plots showing CD1d-endo and CD1d-α-GalCer tetramer staining of TRAV26\u003csup\u003e+\u003c/sup\u003e, and TRAV26\u003csup\u003e-\u003c/sup\u003e clones. Type I NKT TCR\u003csup\u003e+\u003c/sup\u003e clone NKT15 and non CD1d-reactive TCRs (T29_E-top/3C4-bottom) were included as controls. Bar graphs summarise CD1d-tetramer mean fluorescence intensity (MFI) for: HEK293T-transfections (left), from \u003cem\u003en\u003c/em\u003e=3 (VD3G8), \u003cem\u003en\u003c/em\u003e=5 (T14), \u003cem\u003en\u003c/em\u003e=3 (T26A) and \u003cem\u003en\u003c/em\u003e=2 (T26B/iT26/NKT15/T29_E) independent experiments; or SKW3.b2m\u003csup\u003e-/-\u003c/sup\u003e (right), from \u003cem\u003en\u003c/em\u003e=6 (VD3G8), \u003cem\u003en\u003c/em\u003e=4 (T14/iT26, with \u003cem\u003en\u003c/em\u003e=3 for CD1d-a-GalCer), \u003cem\u003en\u003c/em\u003e=9 (T26A, \u003cem\u003en\u003c/em\u003e=8 for CD1d-a-GalCer), \u003cem\u003en\u003c/em\u003e=7 (T26B, with \u003cem\u003en\u003c/em\u003e=6 for CD1d-a-GalCer), and\u003cem\u003e n\u003c/em\u003e=3 (3C4), independent experiments. For \u003cem\u003en\u003c/em\u003e=1 HEK293T experiments staining controls included unconjugated SAV-PE (crosses) or CD1c tetramer-PE (spheres). For SKW3.b2m\u003csup\u003e-/-\u003c/sup\u003e experiments, CD1c tetramer-PE controls were included in \u003cem\u003en\u003c/em\u003e=4 (VD3G8) \u003cem\u003en\u003c/em\u003e=2 (T14) \u003cem\u003en\u003c/em\u003e=6 (T26A) \u003cem\u003en\u003c/em\u003e=5 (T26B) \u003cem\u003en\u003c/em\u003e=3 (iT26) \u003cem\u003en\u003c/em\u003e=6 (NKT15) \u003cem\u003en\u003c/em\u003e=4 (3C4) experiments, or SAV-PE for \u003cem\u003en\u003c/em\u003e=1 (T26A/T26B/iT26/NKT15).\u0026nbsp; (\u003cstrong\u003ee\u003c/strong\u003e) TCR-transduced cell lines were co-cultured with wild type C1R cells (C1R.WT) or CD1d transduced (C1R.CD1d), as well as C1R.β2m\u003csup\u003e-/-\u003c/sup\u003e cells in the presence or absence of α-GalCer (1mg/mL). Bar graphs show CD69 MFI fold increase +/-SEM relative to SKW3.β2m\u003csup\u003e-/-\u003c/sup\u003e alone. Each dot represents an independent experiment (with:without a-GalCer, respectively): \u0026nbsp;\u003cem\u003en\u003c/em\u003e=8:11 (VD3G8), \u003cem\u003en\u003c/em\u003e=8:13 (T14), \u003cem\u003en\u003c/em\u003e=9:12 (T26A), \u003cem\u003en\u003c/em\u003e=8:13 (T26B), \u003cem\u003en\u003c/em\u003e=6:9(iT26), \u003cem\u003en\u003c/em\u003e=7:10(NKT15) in C1R.CD1d co-cultures; or \u003cem\u003en\u003c/em\u003e=4:6(VD3G8), \u003cem\u003en\u003c/em\u003e=5:8(T26A),\u0026nbsp; \u003cem\u003en\u003c/em\u003e=3:3 (iT26), \u003cem\u003en\u003c/em\u003e=4:7 (T26B/T14/NKT15) in C1R.WT co-cultures; or \u003cem\u003en\u003c/em\u003e=3:6 (iT26), \u003cem\u003en\u003c/em\u003e=3:4 (T26A/T26B/T14/NKT15) in C1R.β2m\u003csup\u003e-/- \u003c/sup\u003eco-cultures.\u0026nbsp; Experiments shown in blue/grey/green/pink are from the series of experiments shown in Fig. S3a and those in orange/red/yellow are from Fig. S3b (isotype-control treated C1R.CD1ds, performed alongside C1R.β2m).\u003c/p\u003e","description":"","filename":"Fig25nov.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/4042530f33180a47e81bf0ba.png"},{"id":97671508,"identity":"25af5afc-1c82-4075-be1d-6eeb4314a13e","added_by":"auto","created_at":"2025-12-08 09:32:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1662941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTCR trap determination of T26A TCR-CD1d-endo complexes.\u003c/strong\u003e (\u003cstrong\u003ea\u003c/strong\u003e) CD1d alone, T26A TCR alone or CD1d-TCR complexes were introduced to size exclusion chromatography. For CD1d and TCR runs, fractions eluting earlier than monomers (green box) were enriched for CD1d-TCR dimers, as confirmed by polyacrylamide gel electrophoresis, and were pooled to optimize lipids entering mass spectrometry experiments (MS). Fractions were normalized to protein input and then subjected to lipid elution. The eluents were analysed by the negative mode nano-electrospray (middle) and HPLC–Quadruple Time of Flight–MS (right) to identify ions and mass chromatograms identifiable as SMs (red) and PCs (blue) with the indicated m/z values, total chain length (C) and unsaturations (0, 1, 2). Data is representative of \u003cem\u003en=3\u003c/em\u003e independent experiments involving T26A. (\u003cstrong\u003eb\u003c/strong\u003e) The same analysis for CD1d-T26B, CD1d-T14, and CD1d-VD3G8 TCR complexes was performed for one or two trap experiments, respectively. (\u003cstrong\u003ec\u003c/strong\u003e) TRAV26\u003csup\u003e+ \u003c/sup\u003e(T26A, T26B) and TRAV26\u003csup\u003e- \u003c/sup\u003e(T14, VD3G8) CD1d-endo-reactive type II NKT TCR-transduced SKW3.β2m\u003csup\u003e−/−\u003c/sup\u003e cell lines, were stained with CD1d-tetramers, each exogenously treated with a different ligand. The type I NKT15 TCR and VD1G9 ClPPBF-reactive TCR clones as controls. The fold variation in CD1d tetramer mean fluorescence intensity (MFI) ± SEM, relative to CD1d-endo is shown, from \u003cem\u003en=3\u003c/em\u003e independent experiments, each represented by a single point, except for T14 staining with CD1d-LPE, NKT15 with CD1d-PI, VD3G8 stains with all CD1d-tetramers or conditions involving CD1d-SM24:1 where \u003cem\u003en\u003c/em\u003e=2.\u003c/p\u003e","description":"","filename":"Fig3t26.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/2fea947822a45810260ff0d7.png"},{"id":97671862,"identity":"05b89868-4af5-4508-9d29-f587166bdf2f","added_by":"auto","created_at":"2025-12-08 09:33:11","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1118487,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAffinity measurements of type II NKT TCRs.\u003c/strong\u003e Surface plasmon resonance (SPR) of soluble T14, T26A, T26B and NKT15 NKT TCRs against CD1d-endo, CD1d-GD3, CD1d-sulfatide and CD1d-α-GalCer. The shown sensograms are representative of one experiment performed in duplicate. The resulting Kd ± SEM values are derived from \u003cem\u003en=6\u003c/em\u003eindependent experiments (T26A, T26B and T14 TCRs) and \u003cem\u003en=3\u003c/em\u003e (NKT15 TCR) and each performed in duplicate.\u003c/p\u003e","description":"","filename":"Fig.4.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/bd2376a4089f757233b7383a.png"},{"id":97672031,"identity":"b7967e35-d3c8-44a4-9ab8-132220608b47","added_by":"auto","created_at":"2025-12-08 09:33:48","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2114600,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverview of the mouse type II XV19, human type II T26A and human type I NKT15 NKT TCRs-CD1d ternary complexes.\u003c/strong\u003e Crystal structure of the (\u003cstrong\u003ea\u003c/strong\u003e) human T26A TCR-CD1d-endo (SM C40:2 modelled), (\u003cstrong\u003eb\u003c/strong\u003e) T26A TCR-CD1d-GD3, (\u003cstrong\u003ec\u003c/strong\u003e) mouse XV19 TCR-CD1d-α-GalCer (PDB code: 4EI5) and (\u003cstrong\u003ed\u003c/strong\u003e) human NKT15 TCR-CD1d-α-GalCer (PDB code: 2PO6) ternary complexes. The top panels show a cartoon representation of each ternary complex, middle panels depict a top view of the CD1d-binding cleft and the bottom panels illustrate the TCR footprints on the CD1d-lipid molecular surface. Top panels: the CD1d and β2-microglobulin (β2m) molecules are coloured in grey and gold, respectively. XV19 TCRα, light green; XV19 TCRβ, light purple; T26A TCRα, yellow; T26A TCRβ, green; NKT15 TCRα, light brown; NKT15 TCRβ, light blue. The CDR loops are coloured as follows: CDR1α, pink; CDR2α, magenta; CDR3α, orange; CDR1β, blue; CDR2β, lemon green; CDR3β, cyan. The carbon atoms of the lipids, sphingomyelin (SM 40:2), GD3, sulfatide and α-GalCer are coloured violet, orange, pale yellow and yellow spheres, respectively.\u003cstrong\u003e \u003c/strong\u003eThe oxygen and nitrogen atoms are coloured red and blue, respectively. Middle panels:\u003cstrong\u003e \u003c/strong\u003ethe lipids are shown as spheres and coloured as in top panels. The center of mass of the respective TRAV and TRBV variable domains are shown as black spheres. Bottom panels: the molecular surface of CD1d is coloured in light grey. Lipids are in black. CDRs TCR contact sites are coloured as in top panels.\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/92b9b53eb3b970b57afe3a18.png"},{"id":97670137,"identity":"81538080-ee94-45db-9a54-dae6a66c141a","added_by":"auto","created_at":"2025-12-08 09:29:46","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":2155834,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMolecular interactions at the T26A TCR/CD1d-SM.\u003c/strong\u003e (\u003cstrong\u003ea\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003e2Fo-Fc\u003cstrong\u003e \u003c/strong\u003eelectron density map of SM contoured at 0.8σ level. SM is shown as blue sticks. (\u003cstrong\u003eb-d\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003eMolecular interactions of the T26A CDR1α (pink), CDR2α (purple), CDR3α (orange), CDR3β (cyan) and FWα (brown) with CD1d-SM. (\u003cstrong\u003ee\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003e2Fo-Fc\u003cstrong\u003e \u003c/strong\u003eelectron density map of GD3 (partially modelled) contoured at 0.8σ level with GD3 shown as orange sticks. (\u003cstrong\u003ef\u003c/strong\u003e)\u003cstrong\u003e \u003c/strong\u003eMolecular interactions of T26A TCR with GD3. For clarity, the α1- and α2-helices of CD1d are shown as cartoon representation and coloured in light grey.\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/f2c82c086d00f1ae708b9d88.png"},{"id":97512949,"identity":"c41ba020-ec8d-4314-8eef-7230be7a5766","added_by":"auto","created_at":"2025-12-05 09:32:23","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1670005,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCD1d docking modes of CD1d-endo reactive type II NKT cells\u003c/strong\u003e. TRAV26\u003csup\u003e+ \u003c/sup\u003e(T26A, T26B and iT26), and TRAV26\u003csup\u003e- \u003c/sup\u003e(T14 and VD3G8) CD1d-endo reactive NKT TCR-transduced SKW3.β2m\u003csup\u003e−/−\u003c/sup\u003e cell lines were co-cultured for 16 h with C1R cells each transduced with a single (Ala) mutated version of CD1d. The responses by the type I NKT15 TCR-expressing cell line were analysed as a control. The level of activation (CD69-fold change in comparison to TCR-transduced cell lines alone) elicited by each mutant line is normalized to the response elicited to \u003cem\u003ewild type\u003c/em\u003e (WT) C1R.CD1d. Data depict mean ± SEM from \u003cem\u003en\u003c/em\u003e=3 independent experiments for NKT15, T26A and iT26, \u003cem\u003en\u003c/em\u003e=4 for T26A, T26B and \u003cem\u003en\u003c/em\u003e=5 for T14. Corresponding CD1d molecular surface maps (Protein Data Bank code: LZT4) are shown to the right of each graph, depicting residues that, when mutated, had no effect (dark grey), a minor (\u0026lt;25%, red), major (\u0026lt;75%, orange) fold decrease, or a fold increase (\u0026gt;50%, green) in CD69 MFI relative to WT CD1d.\u003c/p\u003e","description":"","filename":"Fig7.png","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/a0a713040b3c4da000f5fa55.png"},{"id":98438874,"identity":"581a984d-cb6e-4b12-bd87-fb1af05fe6a9","added_by":"auto","created_at":"2025-12-17 17:00:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13991950,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/07405de1-d288-4034-a422-e9b92a8db3f0.pdf"},{"id":97671812,"identity":"8b4d01c4-d5d4-45b6-80a6-94216e896cb1","added_by":"auto","created_at":"2025-12-08 09:33:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2022598,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental material\u003c/p\u003e","description":"","filename":"PoaandHarpurSupplementaryinformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7004764/v1/4a1807021797a2073a44a073.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nD. I. G and C. F. A hold two patents on CD1-targetting for immune modulation.","formattedTitle":"\u003cp\u003eA conserved human population of TRAV26\u003csup\u003e+\u003c/sup\u003e type II Natural Killer T cells solely recognise CD1d\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eNatural Killer T (NKT) cells recognise lipid-based antigens (Ags) presented by the monomorphic MHC class I-like molecule CD1d. NKT cells are generally classified into two main groups, type I and II NKT cells \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Most studies have focussed on type I NKT cells, which express an evolutionary conserved public T cell receptor (TCR) repertoire in humans, defined by an invariant \u003cem\u003eTRAV10-TRAJ18\u003c/em\u003e\u003csup\u003e+\u003c/sup\u003e TCRα chain paired with \u003cem\u003eTRBV25-1\u003c/em\u003e\u003csup\u003e+\u003c/sup\u003e TCRβ chains, that confers co-recognition of a prototypical glycolipid Ag known as α-galactosylceramide (α-GalCer) and related hexosyl ceramides when bound to CD1d \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The use of CD1d-α-GalCer tetramers has enabled extensive research to characterise the phenotypic profile and function of type I NKT cells \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eType II NKT cells were identified circa 30 years ago in mice as CD4\u003csup\u003e+\u003c/sup\u003e T cells that do not recognize MHC class II \u003csup\u003e4, 5\u003c/sup\u003e, or as CD1d-reactive cells that do not require CD1d recycling to endosomes\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Those studies suggested that type II NKT cells express diverse TCR genes, distinct from the semi-invariant TCR characteristic of type I NKT cells, and are therefore commonly described as \u0026lsquo;diverse\u0026rsquo; NKT cells \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. In contrast to type I NKT cells, type II NKT cells do not recognize α-GalCer but can be activated by other CD1d-bound lipid-based Ags including sulfatides and phospholipids as well as small molecules \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Type II NKT cells appear to play a unique role in the immune system \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, with some studies in humans suggesting opposing roles to type I NKT cells \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Type II NKT cells are comprised of specialized subsets capable of monitoring biological processes that impact on lipid metabolism and consequently, on the self-lipids bound to CD1d \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. These cells are associated with, or implicated in, various diseases such as hepatitis, ulcerative colitis, and cancer \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In humans, type II NKT cells appear to outnumber type I NKT cells \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. However, the paucity of reagents to clearly identify type II NKT cells has left fundamental questions unanswered that include the identity of immunodominant Ags, TCR patterns, the underlying mechanisms that regulate their numbers and the molecular mechanism of Ags recognition \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eInsights have been gained into the molecular mechanism that underpins the recognition of CD1d-lipid complexes by human and mouse type I NKT TCRs \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e as well as mouse type II NKT TCRs \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e and \u0026lsquo;atypical\u0026rsquo; NKT cells \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. These studies led to the fundamental principle that underscored the NKT TCR co-recognition paradigm of CD1d-lipid complexes whereby the NKT TCR contacted both CD1d and the presented Ag\u003csup\u003e3\u003c/sup\u003e. However, our understanding of the molecular mechanism that underpins the recognition of CD1d-lipid by human type II NKT TCRs remains less clear.\u003c/p\u003e\u003cp\u003eHere, using human CD1d tetramers presenting endogenous lipids, we identify a population of public type II NKT cells that express a TRAV26\u003csup\u003e+\u003c/sup\u003e TCRa chain. Lipidomic scanning of Ags contained within CD1d-TRAV26\u003csup\u003e+\u003c/sup\u003e TCR complexes revealed a diverse array of lipids, and structural determination of the ternary complex showed that the TCR contacted CD1d in an Ag-independent manner.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cb\u003eIdentification of human CD1d-endo-reactive NKT cells.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEarly studies suggested that type II NKT cells can recognise and respond to CD1d carrying endogenous lipids (CD1d-endo) \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Although some target lipid-Ags for type II NKT cells are known, the study of these cells has been hindered by a limited understanding of their target lipid repertoire. To further investigate the antigenic targets and diversity of human type II NKT cells, CD1d-endo tetramers were generated using glycosylation-deficient GnTI\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e Human Embryonic Kidney 293 (HEK293S) cells to express soluble CD1d ectodomains that incorporate a cellular cargo of endogenous lipids during synthesis \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. These CD1d-endo tetramers stained over 0.1% of live CD3\u003csup\u003e+\u003c/sup\u003e T cells within peripheral blood mononuclear cells (PBMCs) from healthy human donors, albeit with varied and often low mean fluorescence intensity (MFI) in many cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea and S1a). After one round of tetramer-associated magnetic enrichment (TAME) \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e using phycoerythrin (PE)-labelled CD1d-endo tetramers, the frequency of the CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e amongst CD3\u003csup\u003e+\u003c/sup\u003e T cells generally yielded more defined populations at proportions ranging up to 13% (Median (M) 0.92%, interquartile range (IQR) 0.3\u0026ndash;1.9%), in contrast to PE-conjugated streptavidin (SAV-PE) negative controls where no clear population was identified (\u003cb\u003eFig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea\u003c/b\u003e). However, it was possible that some of these frequencies may be impacted by non-TCR CD1d ligands such as CD36 family members \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, as suggested by the enrichment of CD3\u003csup\u003e\u0026minus;\u003c/sup\u003e cells capturing the CD1d-tetramer after TAME (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea and S1a-b). To minimise this, for many samples, we used a CD42b exclusion gate to exclude platelets which express high levels of CD36 and/or CD36 blocking antibody prior to staining of some samples.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTo confirm TCR-dependent CD1d-binding specificity, CD3\u003csup\u003e+\u003c/sup\u003e CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were enriched using flow cytometric cell sorting and expanded in culture for 18\u0026ndash;20 days and re-stained with CD1d-endo tetramers. The CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e populations varied widely in frequency (0.035-100%) of CD3\u003csup\u003e+\u003c/sup\u003e cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea) but often formed more distinct clusters (M\u0026thinsp;=\u0026thinsp;0.84%, IQR\u0026thinsp;=\u0026thinsp;0.2\u0026ndash;8.4%), when compared to post-MACS enriched samples. This may be because the expanded cells were devoid of platelets or other cell types that, through cell adhesion and/or trogocytosis, may confer TCR-independent binding with CD1d-tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and S1a) \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells included both αβ and γδ T cells, with γδ T cell frequencies varying widely in the 25 donors analysed. CD1d-endo-tetramer\u003csup\u003e+\u003c/sup\u003e αβ T cells in these cultures (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) were skewed towards CD4\u003csup\u003e+\u003c/sup\u003e single positive (SP) expression (M 80%, IQR 46\u0026ndash;94%), although CD8\u003csup\u003e+\u003c/sup\u003e SP and CD4\u003csup\u003e\u0026minus;\u003c/sup\u003eCD8\u003csup\u003e\u0026minus;\u003c/sup\u003e double negative (DN) populations were also detected at lower frequencies (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Conversely, the CD1d-endo tetramer\u003csup\u003e\u0026ndash;\u003c/sup\u003e conventional T cells had similar frequencies of CD4\u003csup\u003e+\u003c/sup\u003e SP and CD8\u003csup\u003e+\u003c/sup\u003e SP T cells.\u003c/p\u003e\u003cp\u003eBy co-labelling expanded cells with CD1d-endo tetramer and CD1d-α-GalCer tetramer, many CD1d-binding cells (M 80%, IQR 39\u0026ndash;95%) co-stained with both tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). In the three donors shown, representative of 18 analysed this way, the staining pattern revealed distinct T cell clusters that likely reflected the oligoclonality of expanded NKT cells. Most, but not all, clusters showed a positive correlation for staining intensity by both tetramers, suggesting that binding to CD1d occurs regardless of the lipids within the CD1d cleft.\u003c/p\u003e\u003cp\u003eThe functional potential of expanded cells was also investigated. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells expressed tumour necrosis factor (TNF) and interferon-g (IFNg) (mean 66% and 26%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee), and cytokine production was detected in both CD8\u003csup\u003e\u0026minus;\u003c/sup\u003e and CD8\u003csup\u003e+\u003c/sup\u003e cells (\u003cb\u003eFig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ec\u003c/b\u003e). While some CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells co-produced these cytokines (mean 20%), some produced either one or the other (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee). IL-13 was only detected in a small subset of CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells in some donors, in contrast to CD1d-endo tetramer\u003csup\u003e\u0026minus;\u003c/sup\u003e cells where IL-13 was more frequently detected (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee). Thus, type II NKT cell populations capable of producing pro-inflammatory cytokines are readily identified among human donors by CD1d-endo tetramers with no defined exogenously loaded antigen.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTRAV26 TCR bias amongst human CD1d-endo-reactive T cells.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo characterise the TCR repertoire of the populations labelled by CD1d-endo tetramers, single CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were index sorted from \u003cem\u003ein vitro\u003c/em\u003e expanded cultures and their TCR sequences were determined \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Paired TCRα and TCRβ, or TCRδ and TCRγ chain-transcripts were determined for cells sorted as αβ T cells or γδ T cells (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). None of the sorted T cell clones contained the canonical TCR usage that define type I NKT TCRs. Instead, they exhibited a varied, yet biased, range of γδ and αβ TCR chains (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea-b \u003cb\u003eand\u003c/b\u003e Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Almost all γδ TCRs analysed incorporated \u003cem\u003eTRDV1\u003c/em\u003e genes (17 of 18 Vδ sequences derived from 11 donors (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), in line with previous studies that described Vd1\u003csup\u003e+\u003c/sup\u003e γδ T cells recognizing CD1d \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e and CD1c \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Unexpectedly, within the αβ TCRs, there was a strong bias towards TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs, with ~\u0026thinsp;65% of αβ TCRs within CD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells from 11 donors utilising \u003cem\u003eTRAV26-\u003c/em\u003e2 gene segments. In addition, cells from 5 donors also utilised \u003cem\u003eTRAV26-1\u003c/em\u003e, which differs from \u003cem\u003eTRAV26-2\u003c/em\u003e by four germline encoded amino acids, as well as one amino acid in the CDR3α loop (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Further, \u003cem\u003eTRAV26-2 gene\u003c/em\u003e segments were often associated with \u003cem\u003eTRAJ48\u003c/em\u003e in 17 of 39 TCRs (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), although other TRAJ gene-rearrangements were also detected, including \u003cem\u003eTRAJ42\u003c/em\u003e in 6 of 39 TCRs, \u003cem\u003eTRAJ23\u003c/em\u003e in 5 of 39 TCRs and \u003cem\u003eTRAJ45\u003c/em\u003e in 4 of 39 TCRs (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Type II NKT cells possessing \u003cem\u003eTRAJ48\u003c/em\u003e genes almost exclusively rearranged with \u003cem\u003eTRAV26\u003c/em\u003e\u003csup\u003e+\u003c/sup\u003e, with 17 encoded by \u003cem\u003eTRAV26-2\u003c/em\u003e and one by \u003cem\u003eTRAV26-1\u003c/em\u003e. Moreover, a conserved CDR3α involving the insertion of the same amino acid (G in position 6) in the N-region during rearrangements between \u003cem\u003eTRAV26-2\u003c/em\u003e and \u003cem\u003eTRAJ48\u003c/em\u003e genes was identified in 5 donors across 5 independent experiments (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), demonstrating public conservation of the CDR3a sequence. Notably, this same \u003cem\u003eTRAV26-2\u0026ndash;TRAJ48\u003c/em\u003e rearrangement had also been reported in a single NKT cell clone isolated \u003cem\u003evia\u003c/em\u003e a different approach \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Another conserved motif was detected in positions 6 and 7 of the TRAV26-2 CDR3a sequences, where proline was also often seen at position 6, typically accompanied by bulky residue at position 7 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In contrast to the conserved TCRα chain, the TCRβ gene usage was highly diverse, as were the CDR3β sequences and lengths (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003ePaired gd TCR sequences of CD1d-endo tetramer\u0026thinsp;+\u0026thinsp;single-sorted cells\u003c/b\u003e IMGT TCR gene nomenclatures and associated complementary determining region (CDR) loop amino acid sequences are shown for γδ T cells sorted with CD1d-endo tetramers post-sort/expansion in culture for 21 d as per Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea. The number of observations (obs. column) as well as intra-donor frequency at which each unique clonotype was observed amongst total amplified gd TCRs are shown from an analysis of 11 donors. A total of three sorting experiments were performed. Red residues are either partially or fully non-germline encoded. XX means undetermined. Sequences selected to generate γδ TCR-transduced NKT cell clones, are given a clone name. Amino acid positions: CDR1-IMGT (27 to 38), CDR2-IMGT (56 to 65), and CDR3 (105 to 117)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"19\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDonor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCDR1d\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCDR2d\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u003cp\u003eCDR3d\u003c/p\u003e\u003cp\u003e(non germline)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCDR1g\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003eCDR2g\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c17\" namest=\"c15\"\u003e\u003cp\u003eCDR3g\u003c/p\u003e\u003cp\u003e(non germline)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c18\"\u003e\u003cp\u003eObs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c19\"\u003e\u003cp\u003e% within donor\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVD3G8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTVYS\u0026hellip;NPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eGDN\u0026hellip;SRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eRGTGGYPWA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAQLFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV8*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ2*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVEN\u0026hellip;AVY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDSY\u0026hellip;NSRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLLYPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLRVGWGR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVIN\u0026hellip;AFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;NSKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eXXXX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLAFFT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV8*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1/2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVEN\u0026hellip;AVY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDSY\u0026hellip;NSRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRSR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNYYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSGIRLY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV8*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJP1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVEN\u0026hellip;AVY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDSY\u0026hellip;NSRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWDR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePGN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTTGWFKIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eQVVYWGIRTM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJP2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVIN\u0026hellip;AFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;NSKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eSPPG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSDWIKTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLPGGYAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eEGS\u0026hellip;TGY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYGSY\u0026hellip;TSSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePIPGVS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD2/TRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDPASYPFVLGD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJP2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVIN\u0026hellip;AFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;NSKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eSPPG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSDWIKTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD2/TRDD3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDPASYPFVLGD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSRTGGYARG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eEGS\u0026hellip;TGY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYGSY\u0026hellip;TSSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePVLN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDSRRDKAY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*01/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVIN\u0026hellip;AFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;NSKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eGAQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDPGVTH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVTN\u0026hellip;TFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;TARD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWDR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eLGAD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eRRIRGVN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eEGS\u0026hellip;NGY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDSY\u0026hellip;NSKV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWDG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNGYWG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eVTN\u0026hellip;TFY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYDVS\u0026hellip;TARD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePYP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLRVLGA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLTAQLFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eEGS\u0026hellip;TGY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYGSY\u0026hellip;TSSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eGLQKGS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTSYGGTGGYGVD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eRYLPTA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRGV9*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRGJ1*02/ TRGJ2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eGITI\u0026hellip;SATS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eISYD\u0026hellip;GTV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCALWE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYKKLF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRDV1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRDJ1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTRDD3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTSWW\u0026hellip;SYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQG\u0026hellip;S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCALG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGLIYKGDSASLGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003ePaired ab TCR sequences of CD1d-endo tetramer\u0026thinsp;+\u0026thinsp;single-sorted cells\u003c/b\u003e IMGT TCR gene nomenclatures and associated complementary determining region (CDR) loop amino acid sequences are shown for ab T cells sorted with CD1d-endo tetramers post-sort/expansion in culture for 21 d as per Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea. The number of observations (obs. column) as well as intra-donor frequency at which each unique clonotype was observed amongst total amplified ab TCRs are shown from an analysis of 14 donors. Sequences in bold contain the invariant TRAV26-TRAJ48 rearrangement. A total of eight single-cell sorting experiments were performed. Red residues are either partially or fully non-germline encoded. Sequences selected to generate αβ NKT cell clones are given a clone name. Amino acid positions: CDR1-IMGT (27 to 38), CDR2-IMGT (56 to 65), and CDR3 (105 to 117).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"19\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDonor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCDR1a\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCDR2a\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eCDR3a\u003c/p\u003e\u003cp\u003e(non germline)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCDR1b\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003eCDR2b\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c17\" namest=\"c15\"\u003e\u003cp\u003eCDR3b\u003c/p\u003e\u003cp\u003e(non germline)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c18\"\u003e\u003cp\u003eObs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c19\"\u003e\u003cp\u003e% within donor\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eiT26\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4A\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eTRAV26-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTRAJ48*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eTISG\u0026hellip;TDY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eGLT\u0026hellip;SN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eCILRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eG\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eFGNEKLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eTRBV6-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003eTRBJ2-1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003eTRBD1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eMNH\u0026hellip;EY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u003cb\u003eSVG\u0026hellip;EGT\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e\u003cb\u003eCASSY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e\u003cb\u003eQNKGF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e\u003cb\u003eNEQFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e\u003cb\u003e39\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ44*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;NEY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLK\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIVR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eASWR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTGTASKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ13*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNIAT\u0026hellip;NDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGYK\u0026hellip;TK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNSGGYQKVTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV28-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMDH\u0026hellip;EN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSYD\u0026hellip;VKM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eFTGGAEGF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eEAFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e4A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTRAV13-1*01\u003c/p\u003e\u003cp\u003eor\u003c/p\u003e\u003cp\u003eTRAV13-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTRAJ9*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDSA\u0026hellip;SNY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIRSN\u0026hellip;VGE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNTGGFKTIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTRBV5-5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSGH\u0026hellip;KS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eYYE\u0026hellip;KEE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCASSL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGGTVL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNTEAFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNSA\u0026hellip;SDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIRSN\u0026hellip;MDK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV8-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ49*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSSY\u0026hellip;SPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYTSA\u0026hellip;ATLV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCVVS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTGNQFYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMGH\u0026hellip;RA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYSY\u0026hellip;EKL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eDPSGRY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e28.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV27*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ23*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSVF\u0026hellip;SS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eVVTG\u0026hellip;GEV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eVS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIYNQGGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLGH\u0026hellip;NA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNF\u0026hellip;KEQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eERXA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYNEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSSG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMGH\u0026hellip;RA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYSY\u0026hellip;EKL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eLPRLAGGA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eETQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4G\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eTRAV26-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTRAJ48*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eTISG\u0026hellip;TDY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eGLT\u0026hellip;SN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eCILRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eG\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eFGNEKLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eTRBV5-6*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003eTRBJ2-6*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003eTRBD1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eSGH\u0026hellip;DT\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u003cb\u003eYYE\u0026hellip;EEE\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e\u003cb\u003eCASSL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e\u003cb\u003eGTTP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e\u003cb\u003eSGANVLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV19*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLNH\u0026hellip;DA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSQI\u0026hellip;VND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eTKVGGLSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003ePQHF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAPF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV28*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMDH\u0026hellip;EH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSYD\u0026hellip;VKM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNTPGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eGYTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ45*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eYSGGGADGLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4K\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;NEY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLK\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIVRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eVV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV6-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMNH\u0026hellip;NS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSAS\u0026hellip;EGT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePGWTGP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNYGYTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e58.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ41*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;NEY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLK\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNSGYALNF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV6-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMNH\u0026hellip;EY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSVG\u0026hellip;EGT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePGGXXE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGAPY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV6-5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMNH\u0026hellip;EY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSVG\u0026hellip;AGI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRGN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eEQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e12.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ23*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIYNQGGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV20-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-6*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eDFQ\u0026hellip;ATT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSNEG\u0026hellip;SKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eARLEGP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eGANVLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePGF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV7-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSGH\u0026hellip;TA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eFQG\u0026hellip;NSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eASPGAXVV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eETQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNQVY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV12-4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSGH\u0026hellip;DY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eFNN\u0026hellip;NVP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eFITGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eLFGELFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e14.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV10*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ17*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eVSP\u0026hellip;FSN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMTFS\u0026hellip;ENT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCVVS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAAGNKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMGH\u0026hellip;RA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYSY\u0026hellip;EKL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eAKNIQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV29/DV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ54*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNSM\u0026hellip;FDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eISSI\u0026hellip;KDK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIQGAQKLVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ32*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eFGG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGATNKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV27*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eUNCLEAR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT26B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV13-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003ePRH\u0026hellip;DT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eFYE\u0026hellip;KMQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eEGL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT26A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ40*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGWG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGTYKYIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV19-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLNH\u0026hellip;DA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSQI\u0026hellip;VND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eTSVGRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ29*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSGNTPLVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e26.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV24-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eKGH\u0026hellip;DR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSFD\u0026hellip;VKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eEDXLGW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTEAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e6.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV20-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eDFQ\u0026hellip;ATT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSNEG\u0026hellip;SKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRDREGA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYGYTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e44.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ23*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIYNQGGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e11.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ36*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTGANNLFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV30*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-6*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eGTS\u0026hellip;NPN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSVG\u0026hellip;IG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAWS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eVAGGVIA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSYNSPLHF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e11.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ54*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFGKF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eQGAQKLVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGWA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ30*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDDKIIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e85.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV29/DV5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNSM\u0026hellip;FDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eISSI\u0026hellip;KDK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePTIS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV14/DV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ43*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSDQ\u0026hellip;SYG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eQGSY\u0026hellip;DEQN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAMRE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNNDMRF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSNH\u0026hellip;LY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eFYN\u0026hellip;NEI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eGLAGA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYEF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV38-2/DV8*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ33*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSES\u0026hellip;DYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eQEAY\u0026hellip;KQQN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDSNYQLIW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV24-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eKGH\u0026hellip;DR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSFD\u0026hellip;VKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eAPARLD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV35*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ34*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSIF\u0026hellip;NT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLYKA\u0026hellip;GEL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSYNTDKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV28*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-5*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMDH\u0026hellip;EN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSYD\u0026hellip;VKM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eDLTGQG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eETQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCA4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV38-2/DV8*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ52*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSES\u0026hellip;DYY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eQEAY\u0026hellip;KQQN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNAGGTSYGKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eQAPFN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV10-3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eENH\u0026hellip;RY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSYG\u0026hellip;VKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCAISE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eSSAAGR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTEAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAPL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV19*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLNH\u0026hellip;DA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSQI\u0026hellip;VND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNHRVGW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTGELFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e17.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eCH5\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eTRAV26-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTRAJ48*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eTISG\u0026hellip;TDY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eGLT\u0026hellip;SN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eCIRLD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eG\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eFGNEKLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eTRBV19*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003eTRBJ2-7\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003eTRBD1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eLNH\u0026hellip;DA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u003cb\u003eSQI\u0026hellip;VND\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e\u003cb\u003eCASS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e\u003cb\u003eRGDRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e\u003cb\u003eYEQYEF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e20.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ34*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePWD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTDLKIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV3-1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLGH\u0026hellip;DT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNN\u0026hellip;KEL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eQTAT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNTGELFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV29*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ26*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNSM\u0026hellip;FDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eISSI\u0026hellip;KDK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEILK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGQNFVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV20-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eDFQ\u0026hellip;ATT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSNEG\u0026hellip;SKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eSYSAGHW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e10.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV17*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ11*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSI\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIRSN\u0026hellip;ERE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCATD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGYSTLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ37*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;NEY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLK\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIVRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNTGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLGH\u0026hellip;NA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNF\u0026hellip;KEQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eADF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSYEQYEF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ20*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;NEY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLK\u0026hellip;NN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIVRV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAPPF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNDYKLSF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV6-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ43*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFGL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNNDMRF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV10-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMNH\u0026hellip;NS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSAS\u0026hellip;EGT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRFPW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNTEAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ23*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIYNQGGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV14*01/*02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eWSH\u0026hellip;SY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSAA\u0026hellip;ADI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRLARY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ45*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFRVY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eYSGGGADGLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV9*02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSGH\u0026hellip;DN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eFVK\u0026hellip;ESK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eLRDRVWRKEG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTDTQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGAPG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSGD\u0026hellip;LS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNN\u0026hellip;GEE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eVAPGPAK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSTDTQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e4.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ23*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIYNQGGKLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e4.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eCH8\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eTRAV26-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTRAJ48*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eTISG\u0026hellip;TDY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eGLT\u0026hellip;SN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eCILRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eG\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eFGNEKLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eTRBV27*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ57*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGWGLV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTQGGSEKLVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV9*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003eTRBJ1-1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003eTRBD1*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003eMNH\u0026hellip;EY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u003cb\u003eSMN\u0026hellip;VEV\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e\u003cb\u003eCAS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e\u003cb\u003eTPFRTGWS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e\u003cb\u003eEAFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ42*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNYGGSQGNLIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV27*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSGD\u0026hellip;LS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNN\u0026hellip;GEE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eGLRDH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eEAFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e64.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCH8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV41*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ49*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eVGI\u0026hellip;SA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLSS\u0026hellip;GK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGNQFYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-7*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMNH\u0026hellip;EY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSMN\u0026hellip;VEV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePTGGPLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYEQYEF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV14/DV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ49*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSDQ\u0026hellip;SYG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eQGSY\u0026hellip;DEQN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAMRE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGYL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNTGNQFYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV24-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ45*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGFLM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eYSGGGADGLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV3-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eKGH\u0026hellip;DR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSFD\u0026hellip;VKD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCATSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRTG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eYNEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e19.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ45*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGWGM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eYSGGGADGLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV20-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-3*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLGH\u0026hellip;DT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYNN\u0026hellip;KEL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePRDRIQG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTDTQYF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV41*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ45*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eVGI\u0026hellip;SA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLSS\u0026hellip;GK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSGGGADGLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTRBV4-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ2-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eDFQ\u0026hellip;ATT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSNEG\u0026hellip;SKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCSAR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eLAAD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eSYNEQFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e12.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ40*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILRD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGWG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGTYKYIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTRBJ1-1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTRBD1*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eMGH\u0026hellip;RA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYSY\u0026hellip;EKL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eCASS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003ePQPWGNAY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eTEAFF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV14/DV4*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ27*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTSDQ\u0026hellip;SYG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eQGSY\u0026hellip;DEQN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCAMR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNTNAGKSTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTRAV26-2*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTRAJ48*01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTISG\u0026hellip;TDY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGLT\u0026hellip;SN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCILR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAPFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFGNEKLTF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMSC4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eTRAV26-2*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTRAJ48*01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eTISG\u0026hellip;TDY\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eGLT\u0026hellip;SN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eCILRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eG\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eFGNEKLTF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e25.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSingle-cell index-sorting analysis of TCR gene expression revealed that the subpopulations co-staining with both CD1d-endo and CD1d-α-GalCer tetramers mainly comprised TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs, indicated by red dots in the two representative donors (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). These cells were also CD4\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;100%) in 5 out of 6 donors analysed over 5 different index-sorting experiments, while in one donor, they were CD4\u003csup\u003e\u0026minus;\u003c/sup\u003eCD8\u003csup\u003e\u0026minus;\u003c/sup\u003eDN or CD4\u003csup\u003e\u0026minus;\u003c/sup\u003eCD8\u003csup\u003elow\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). In summary, the human CD1d-endo-reactive population harbours a public type II NKT repertoire characterised by biased \u003cem\u003eTRAV26\u003c/em\u003e\u003csup\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sup\u003e TCR usage and a semi-conserved CDR3a motif, often expressed as a canonical \u003cem\u003eTRAV26-2-TRAJ48\u003c/em\u003e rearrangement.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTRAV26\u003c/b\u003e\u003csup\u003e\u003cb\u003e+\u003c/b\u003e\u003c/sup\u003e \u003cb\u003eTCRs directly recognise CD1d.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo test the specificity of the CD1d-endo-reactive TCRs, five paired TCRs that included three TRAV26\u003csup\u003e+\u003c/sup\u003e clones (\u0026ldquo;T26A\u0026rdquo;, \u003cem\u003eTRAV26-2-TRAJ40 TRBV19\u003c/em\u003e, \u0026ldquo;T26B\u0026rdquo; \u003cem\u003eTRAV26-2-TRAJ42 TRBV13-1\u003c/em\u003e and \u0026ldquo;iT26\u0026rdquo;, \u003cem\u003eTRAV26-2-TRAJ48 TRBV6-2\u003c/em\u003e), and two TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e clones (an αβ TCR identified in \u003csup\u003e7\u003c/sup\u003e, \u0026ldquo;T14\u0026rdquo;, \u003cem\u003eTRAV14-TRAJ34 TRBV19\u003c/em\u003e, and a γδ TCR \u0026ldquo;VD3G8\u0026rdquo;, \u003cem\u003eTRDV3-TRDJ2 TRG8\u003c/em\u003e) (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were transiently transfected into HEK293T cells, or transduced β2m-deficient SKW3 cells (SKW3.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e). These two TCR transduced cell systems were assessed for binding CD1d-α-GalCer and CD1d-endo tetramers, in comparison to a control cell line expressing a type I NKT TCR \u0026ldquo;NKT15\u0026rdquo; \u003csup\u003e35\u003c/sup\u003e, or non-NKT controls including the T29_E \u003csup\u003e7\u003c/sup\u003e and the CD1c-reactive clone 3C4 \u003csup\u003e32\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). The five lines stained strongly with CD1d-endo tetramers, with MFIs\u0026thinsp;\u0026gt;\u0026thinsp;45000 in HEK293T or \u0026gt;\u0026thinsp;1000 in SKW3.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), unlike the negative controls. While CD1d-α-GalCer tetramers showed much lower staining of the TRAV26\u0026ndash; lines (typically 10-100-fold less than CD1d-endo), they stained all three TRAV26\u003csup\u003e+\u003c/sup\u003e lines to a similar degree as CD1d-endo tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), reflecting the co-staining profile observed after \u003cem\u003ein vitro\u003c/em\u003e expansion of the parental clones (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). This suggested that the TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e TCRs may detect an undefined mammalian endogenous lipid presented by CD1d, and that a-GalCer can displace this lipid thereby preventing recognition, whereas the TRAV26\u003csup\u003e+\u003c/sup\u003e lines are indifferent to the presence of a-GalCer. As expected, the type I NKT15 TCR line stained far more strongly with CD1d-α-GalCer tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), whereas the CD1d-restricted lines were not stained by SAV-PE alone, nor by CD1c-tetramers conjugated to PE (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), which instead specifically stained the 3C4 control.\u003c/p\u003e\u003cp\u003eTo measure TCR-mediated activation following CD1d binding, NKT TCR-transduced cell lines were co-cultured with Ag-presenting cells with differing levels of CD1d. These included: wildtype C1R cells (C1R.WT) with low CD1d expression, CD1d transductants (C1R.CD1d) with high CD1d expression, or β2m knockout C1R cells (C1R.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e) that lack surface CD1d \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The TCR-transduced lines derived from CD1d-endo sorted cells upregulated the activation marker CD69 when co-cultured with C1R.CD1d, whereas C1R.WT or C1R C1R.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e cells did not cause activation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee). α-GalCer elicited strong responses by the NKT15 cell line using C1R.WT or C1R.CD1d, whereas similar activation was observed in the presence or absence of α-GalCer for TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e or TRAV26\u003csup\u003e+\u003c/sup\u003e lines (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee). Notably, α-GalCer did not block activation of the TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e lines despite blocking CD1d tetramer staining of these lines (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), suggesting that a-GalCer was unable to saturate all CD1d molecules on the C1R Ag-presenting cells in these co-culture conditions. Thus, the newly identified TCRs confer signalling in response to CD1d, regardless of whether α-GalCer is present. Taken together, these data suggest that TRAV26\u003csup\u003e+\u003c/sup\u003e NKT cells bind CD1d in a lipid-independent manner and represent a distinct population of human type II NKT cells.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrapping lipids between CD1d and TCRs.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTwo hypotheses regarding the role of lipids in CD1d-TCR binding were investigated. The first was that TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs bind CD1d in a lipid-independent fashion, reminiscent of what has been reported for CD1a \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e and CD1c \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. The second, supported by studies of known type II NKT cell ligands, sulfatides \u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e and membrane phospholipids \u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, was that some as yet unknown but ubiquitous self-lipid can increase the TCR binding-affinity to CD1d and that a-GalCer can substitute for this lipid. To test these hypotheses, the \u0026lsquo;TCR trap\u0026rsquo; method \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e was employed whereby the soluble TCRs were allowed to form a complex with CD1d-endo that was subsequently purified using size exclusion chromatography, where TCR-bound CD1d molecules can be separated from non-bound CD1d molecules (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). The eluents of CD1d-TCR were then compared to CD1d alone by mass spectrometry analysis to identify the lipids specifically associated with CD1d-TCR binding.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe human CD1d-endo carries a heterogenous cargo of self-lipids that are detectable by nano-electrospray and reversed phase high performance liquid chromatography-mass spectrometry (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Nano-electrospray analysis was conducted on lipids that were eluted from the TCR alone, CD1d alone and CD1d in complex with the two TRAV26\u003csup\u003e+\u003c/sup\u003e αβ TCRs (T26A and T26B), the γδ TCR (VD3G8) and the TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e αβ TCR (T14) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). For TCR alone no clear signals for lipid binding were observed, as expected (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). In contrast, for CD1d alone, there were many \u003cem\u003em/z\u003c/em\u003e signals in negative mode. Similar to recent results with CD1a \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, and other CD1 molecules \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e the strongest signals matched the absolute mass and alkane series patterns for sphingomyelins (SM, \u003cem\u003em/z\u003c/em\u003e 737.6, 765.6, 819.6, 845.6 and 847.6) and some weak signals matched for phosphatidylcholine (PC, \u003cem\u003em/z\u003c/em\u003e 794.6, 904.7, 906.7, 932.7 and 934.7), which are the two most abundant cellular sphingolipid and phospholipid classes, respectively. In contrast to results from a type I NKT TCR-trap study in which the TCR strongly influenced the lipids bound to CD1d \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, CD1d in complex with T26A, T26B, VD3G8 and T14 showed a lipid pattern that was highly similar to CD1d alone. Using HPLC-MS as a more quantitative method that separates individual molecules for detection in very narrow mass windows, once again the distinct nature of each TCR in the four types of CD1d-TCR complexes, did not substantially affect the repertoire of lipids that mediated its binding to CD1d \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Indeed, in all cases, the patterns of lipids in CD1d-TCR complexes matched the patterns of lipids seen for CD1d endo alone (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), maintaining high SM to PC ratio \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Thus, no particular exogenous lipid was required for CD1d-TRAV26\u003csup\u003e+\u003c/sup\u003e TCR complex formation, supportive of the first hypothesis that these TCRs bind in Ag-independent manner.\u003c/p\u003e\u003cp\u003eTo independently assess reactivity towards individual lipid species that include known CD1d-presented Ags that might be under-represented or absent from the mixed cargo of endogenous lipids, (dominated by SMs and PCs that were incorporated into CD1d during its biosynthesis in GnTI\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e HEK293S cells\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea\u0026ndash;b), we generated a panel of CD1d tetramers by exogenously loading secreted CD1d with one of the following CD1d-Ags or controls: phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), sphingomyelin (SM C34:1 or C42:2), sulfatide, lyso-(L)PE, LPC, phosphatidylglycerol (PG), ganglioside GD3, α-GalCer, 3-chlorophenyl-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonate (ClPPBF) \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e or vehicle (tyloxapol) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Each tetramer was tested for staining the type II NKT TCR reporter lines (VD3G8, T14, T26A, T26B) and the control NKT lines that expressed the type I NKT15 TCR and the ClPPBF-reactive type II VD1G9 TCR \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). NKT15 and VD1G9 stained only with tetramers carrying their known cognate Ags and not with CD1d-endo. In contrast, amongst all type II NKT lines that were stained with CD1d-endo tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed), T26A and T26B bound CD1d tetramers at similar intensities, regardless of the ligand exogenously added (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec\u003cb\u003e)\u003c/b\u003e, including the bulky GD3 glycolipid \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e, whereas T14 and VD3G8 stained less with CD1d-α-GalCer tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec), and in line with Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed. Thus, in contrast to other NKT lines tested, lipid replacement within CD1d did not markedly affect CD1d-TRAV26 TCR interactions in these systems.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCD1d binding affinity of type II NKT TCRs.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUsing surface plasmon resonance (SPR), the affinity of the interaction between three soluble type II NKT TCRs towards CD1d-endo and CD1d bearing sulfatide, GD3 or α-GalCer was examined. The T26A TCR bound to CD1d-endo with an affinity of ~\u0026thinsp;7.8 \u0026micro;M and this was not impacted by the type of lipid associated with CD1d, with \u003cem\u003eK\u003c/em\u003e\u003csub\u003eD\u003c/sub\u003e values ranging from 7.8 \u0026micro;M to 10.6 \u0026micro;M (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Similarly, the T26B TCR bound to CD1d-endo or CD1d with each of the three defined lipids with a similar range of affinities (5.8\u0026ndash;15.6 \u0026micro;M) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Conversely, the T14 TCR exhibited a finer specificity to the lipids presented by CD1d (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Here, whilst the T14 TCR bound to CD1d-endo, CD1d-sulfatide and CD1d-GD3 with \u003cem\u003eK\u003c/em\u003e\u003csub\u003eD\u003c/sub\u003e values of 13.5, 20.4 and 41.1 \u0026micro;M, respectively, it did not bind to CD1d-⍺-GalCer (\u003cem\u003eK\u003c/em\u003e\u003csub\u003eD\u003c/sub\u003e \u0026gt;200 \u0026micro;M), in agreement with the lack of CD1d-⍺-GalCer tetramer staining of this line (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed\u003cb\u003e)\u003c/b\u003e. Furthermore, none of the tested ligands, including sulfatide, GD3, SM or ⍺-GalCer, enhanced activation of the type II NKT TCR-transduced cell lines measured by CD69 upregulation, whereas ⍺-GalCer elicited stronger activation of the NKT15 type I NKT TCR line, over that elicited by C1R.CD1d or C1R.WT cells (\u003cb\u003eFig. S3a\u003c/b\u003e). These responses reflected specific NKT TCR-CD1d interactions, as they were blocked by anti-CD1d, whereas the control AF7 MAIT TCR \u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e expressing cells only activated in the presence of 5-OP-RU (\u003cb\u003eFig. S3b\u003c/b\u003e). Collectively, these results suggest that the TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs interact with CD1d with similar affinity irrespective of the lipid bound.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eStructure of the TRAV26\u003c/b\u003e\u003csup\u003e\u003cb\u003e+\u003c/b\u003e\u003c/sup\u003e \u003cb\u003etype II NKT TCR-CD1d-lipid complex.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe determined the crystal structure of the T26A NKT TCR-CD1d-endo ternary complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea \u003cb\u003eand Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e). The T26A NKT TCR docked\u0026thinsp;~\u0026thinsp;100\u0026deg; across the main axis of the CD1d Ag-binding cleft, being positioned over the 'left' side of the platform on the A'-roof of CD1d, sitting closer to the ⍺\u003csub\u003e2\u003c/sub\u003e-helix (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea). This docking position clearly contrasted to type I NKT TCR-CD1d-lipid binding (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed). This 'left-shifted' binding footprint was more reminiscent of the recognition strategy adopted by CD1a autoreactive TCRs \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, CD1d-sulfatide-reactive type II NKT TCRs \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec) and some \u0026lsquo;atypical\u0026rsquo; human NKT TCRs \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e whereby the TCRs contacted CD1d and the lipid presented.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMass spectrometry analysis of the T26A TCR-CD1d-endo demonstrated that although mixed lipids were bound, long chain SM (\u0026gt;\u0026thinsp;C40) appeared to be the major species present (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea\u003cb\u003e).\u003c/b\u003e In line with this, we modelled and refined SM (C40:2) as the bound endogenous lipid into the unbiased electron density that was clearly visible within the CD1 cleft (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ea \u003cb\u003e\u0026amp; Fig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003ea\u003c/b\u003e). The T26A TCR did not directly contact the protruding headgroup of the lipid bound within the CD1d cleft whereby the most proximal residue to SM was located\u0026thinsp;\u0026gt;\u0026thinsp;7\u0026Aring; away (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eb\u003cb\u003e)\u003c/b\u003e. This distal mode of binding can explain why these TCRs seemingly bind to CD1d in a lipid-independent manner and indeed tolerate binding to CD1d carrying lipids with head groups that differ in size and shape (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Thus, the TRAV26A\u003csup\u003e+\u003c/sup\u003e NKT TCR contacts CD1d itself, which breaks the CD1d-lipid co-recognition paradigm.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eStructural basis of TCRa chain bias towards CD1d.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUpon complexation, the buried surface area (BSA) of the T26A NKT TCR-CD1d-endo complex (~\u0026thinsp;600 \u0026Aring;\u003csup\u003e2\u003c/sup\u003e), fell outside the range for type I NKT TCR-CD1d ternary complexes (760\u0026ndash;860 \u0026Aring;\u003csup\u003e2\u003c/sup\u003e) and was significantly lower than the mouse type II NKT TCR-CD1d-lipid complexes (~\u0026thinsp;1000 \u0026Aring;\u003csup\u003e2\u003c/sup\u003e) \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. The TCRα and TCRβ chains of T26A contributed\u0026thinsp;~\u0026thinsp;75% and ~\u0026thinsp;25% of the total BSA at the TCR-CD1d interface, respectively, with both the CDR1α (21% BSA) and CDR2α (16% BSA) loops contributing to the TCR-CD1d interface thereby providing immediate insight into the TRAV26 bias. Conversely, the CDR1β and CDR2β did not interact with the CD1d-endo complex, explaining the broader observation of TRBV gene diversity amongst TRAV26 TCRs (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe CDR1α loop sat peripherally above the α2-helix of CD1d whereby Thr30α interacted with Trp160, Gly164, Thr165 and Gln168 residues of CD1d, while Tyr32α stacked against Glu156 and Trp160 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ec \u003cb\u003eand Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/b\u003e). Ser28α contacted only Gln168 while Gly29α contacted Gly164 and Gln168 of CD1d via van der Waals (VDW) and hydrogen bond interactions, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ec \u003cb\u003eand Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/b\u003e). Within the CDR2α loop, Leu51α, Thr52α and Ser53α contacted Asn163 of CD1d and its N-linked glycans (N-acetylglucosamine, NAG) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ec \u003cb\u003eand Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/b\u003e). Further, the germline encoded framework His49α that precedes the CDR2α loop established a VDW interaction with Glu156 in CD1d (\u003cb\u003eTable \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/b\u003e). Interestingly, Thr30α, Thr52α and Ser53α mediated several contact points with CD1d and were not conserved in \u003cem\u003eTRAV26-1\u003c/em\u003e genes, providing molecular insight for why \u003cem\u003eTRAV26-2\u003c/em\u003e may be over-represented between the two genes amongst CD1d-endo-reactive cells (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe CDR3α and CDR3β loops dominated the interactions at the interface with 35% and 25% BSA, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ed). The CDR3α and CDR3β loops were positioned more centrally over the CD1d binding-cleft. Here, Arg99β from the CDR3β loop plunged into the CD1d-binding cleft to form VDW interactions with Trp153, Thr157 and Trp160, while Pro100β contacted Glu156 of CD1d (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eb). The non-germline encoded Gly-Trp motif, which is conserved in 6 out of the 39 TRAV26-2 clones from 4 distinct donors (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), established multiple contacts with CD1d (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ed). Whereas in 18 of the 39 TRAV26-2 clones, a Phe residue was present at this position, which constitutes a Gly-Phe motif (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Interestingly, this Phe residue was germline-encoded in 7 of the TRAV26-2-TRAJ48\u003csup\u003e+\u003c/sup\u003e clones across 6 donors. The other 11 clones harbouring the Gly-Phe motif were all non-germline encoded (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Conservation of bulky aromatic residues within the CDR3α across 74% of the TRAV26-2\u003csup\u003e+\u003c/sup\u003e clones may be a key structural determinant governing the TCR docking topology. Further, bias towards Phe may also explain the relatively high occurrence of \u003cem\u003eTRAV26-2\u0026ndash;TRAJ48\u003c/em\u003e rearrangements. The G93⍺ residue was also highly prevalent in both motifs, which might be preferentially selected over other larger amino acids to avoid steric clashes with Trp160 and/or CDR3β residues (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ed). This finding aligned with the additional patterns observed for TRAV26-2 isolated sequences in positions 6 and 7 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb \u003cb\u003ebottom\u003c/b\u003e) and emphasized the need for a bulky residue in position 7. Collectively, these results suggested that the germline residues encoded by the \u003cem\u003eTRAV26-2\u003c/em\u003e gene, and the rearrangement of non-germline-encoded structural motifs to Gly-Phe/Trp, played a key role in determining the docking modality adopted by the T26A TCR over the α2-helix A\u0026prime;-roof of CD1d.\u003c/p\u003e\u003cp\u003e\u003cb\u003eA common mode of recognition of self-lipids by the T26A NKT TCR.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eStructural studies on the T26A TCR-CD1d-lipid recognition were extended by loading GD3 into CD1d (\u003cb\u003eFig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003eb)\u003c/b\u003e and determining the crystal structure of the ternary complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The electron density for the bound GD3 was partially visible whereby only the first glucose moiety of the headgroup and both lipid tails could be modelled (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ee \u003cb\u003eand Fig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003ec\u003c/b\u003e). The crystal structure revealed a nearly identical docking mode to that of CD1d-endo complex that was modelled as CD1d-SM (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The majority of the molecular interactions at the T26A NKT TCR-CD1d-GD3 interface were also conserved (\u003cb\u003eFig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003ed-e and Table S3\u003c/b\u003e). Indeed, the T26A NKT TCR did not contact the GD3 lipid, as the most proximal TCR residue, Arg99β from the CDR3β, was 10\u0026Aring; away from the glucose moiety (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ef). Other sphingolipid Ags such as α-GalCer would be expected to produce similar observations (\u003cb\u003eFig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003ef\u003c/b\u003e). Collectively, our structural analysis of the T26A type II NKT TCR suggests a new molecular paradigm for CD1d recognition whereby the type II TRAV26\u003csup\u003e+\u003c/sup\u003e NKT TCR can bind CD1d in a lipid-independent manner.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMolecular footprint of TRAV26 type II NKT TCRs onto CD1d.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eHaving established that lipid Ags had little impact on TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs binding to CD1d, the next step was to assess their functional CD1d docking footprints. Here, C1R cell lines overexpressing wild type CD1d or alanine-substituted CD1d mutants targeting solvent-exposed residues of CD1d \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e were used to test their ability to stimulate the TRAV26\u003csup\u003e+\u003c/sup\u003e and TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e TCR-transduced cell lines (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). CD69 upregulation on the NKT15 TCR control line was inhibited by the alanine mutations of Glu83, Val147, Lys86, and Met87, all positioned near to the F'-portal of CD1d, consistent with our previous results \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e and the \u0026lsquo;right-shifted\u0026rsquo; parallel docking strategy adopted by type I NKT TCR(s) \u003csup\u003e35\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). In contrast, the three TRAV26\u003csup\u003e+\u003c/sup\u003e TCR transduced cell lines were not impacted by those mutations but were inhibited (\u0026gt;\u0026thinsp;75%) by mutations of two CD1d residues Gln62 and Trp160, located distant from the F\u0026prime;-portal, where Ags protrude. These data complement the structural data showing that TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs bind the A\u0026prime;-roof. The impact of the CD1d alanine mutant scan was similar, but not identical, across the three TRAV26 TCR lines. This outcome likely reflects differences in CDR3α and TCRβ chain pairing, and their influence on CD1d-binding.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eActivation of both TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e TCR transduced lines (T14 and VD3G8) was severely impacted by mutations of Trp160 and His68, which sit in the A'-roof of CD1d, in addition to other residues closer to the Ag portal, spanning to the F'-roof. Specifically, T14 was moderately inhibited by mutations of Val72, Thr157, Glu83 and Val147 and VD3G8 impacted by Thr157, Glu83, whereas Arg79Ala mutation led to enhanced activation, suggesting that Arg79 interferes with optimal VD3G8 TCR binding to CD1d. Thus, these TRAV26\u003csup\u003e\u0026minus;\u003c/sup\u003e TCRs appeared to dock more centrally and over the Ag portal, which likely reflects their differences in sensing CD1d-bound ligands (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), unlike the extreme A'-roof CD1d-docking by TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs. Collectively, these data suggest that TRAV26\u003csup\u003e+\u003c/sup\u003e NKT TCRs bind to CD1d in a left-shifted approach and ligand-independent manner.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eCurrently, the CD1d-restricted repertoire is thought to comprise a highly conserved population of type I NKT cells, and a group of diverse type II NKT cells. Here, we identify a public population of type II NKT cells defined by a TRAV26 TCR bias and a conserved CDR3a motif and we provide detailed molecular insight into their mode of lipid-independent CD1d recognition. With wider implementation of CD1 tetramers to systematically investigate TCR repertoires, we are increasingly detecting conserved patterns and public TCR usage for particular CD1-Ag pairs \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, 47, 48, 49\u003c/sup\u003e. A general view emerging from these studies is that NKT cells are not exclusively represented by a public TCR, but instead that non-polymorphic CD1 proteins generate an underlying network of T cells shared across donors, with many conserved families of TCRs and Ags.\u003c/p\u003e\u003cp\u003eThe epitope for the TRAV26 TCR is CD1d itself rather than a defined lipid. Thus, an exposed A'-roof is likely a common or nearly universal epitope in humans, which could account for the several distinct TRAV26-TRAJ48\u003csup\u003e+\u003c/sup\u003e T cell clones seen in every donor tested here. These data connect to a prior study where two distinct \u003cem\u003eTRAV26-2\u003c/em\u003e encoded TCRs (\u003cem\u003eTRAV26-2\u0026mdash;TRAJ48\u003c/em\u003e and \u003cem\u003eTRAV26-2\u0026mdash;TRAJ44\u003c/em\u003e) were reported among 14 \u003cem\u003eTRAV10\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eTRAJ18\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eTRBV25\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sup\u003e TCRs isolated with CD1d-a-GalCer tetramers \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, albeit not recognised as a conserved motif through the strategy employed at the time. The Ag-independent mode of CD1d recognition by germline-encoded TRAV26 TCR residues and a conserved CDR3α motif raises interesting questions about the evolutionary pressures that lead to the conservation of TCRs to act as pattern recognition receptors against CD1d.\u003c/p\u003e\u003cp\u003eThus, our results also suggest that some type II NKT cells might be poised to sense overall changes in surface expression of the Ag-presenting molecule CD1d, rather than the lipid-Ag itself. Accordingly, changes in surface expression levels of CD1d have been shown to impact NKT cell function \u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e and are often associated with infection \u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e, cancer \u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e and autoimmunity \u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e. For example, hepatocytes that are chronically infected with Hepatitis C display high CD1d surface expression relative to healthy tissue or other liver disease, to levels that resemble those of C1R.CD1d transfectants published within the same study to elicit IFN-γ release from intrahepatic CD1d-reactive T cells (Type II NKT) \u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. Similarly, another study demonstrated that CD1d overexpression can be targeted by mouse CD1d-reactive Vγ4\u003csup\u003e+\u003c/sup\u003e T cells, promoting viral myocarditis \u003cem\u003esequela\u003c/em\u003e of coxsackievirus infections \u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e. Whether these physiological contexts can lead to activation of TRAV26\u003csup\u003e+\u003c/sup\u003e NKT cells is an important question for further exploration.\u003c/p\u003e\u003cp\u003eWhilst some type II NKT clones can display lipid-Ag specificity \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e and mount lipid Ag-driven responses \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e, other type II NKT cells also retain the ability to recognise CD1d carrying multiple self-Ags \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e possibly as a strategy to sense early stress signals in an innate-like fashion \u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e. Self-reactive profiles have been reported amongst other CD1-restricted lipid-reactive T cells in humans \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and ligand-independent interactions have been described for CD1a \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e, CD1b \u003csup\u003e\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e, CD1c \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e and CD1d \u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e, and MR1 \u003csup\u003e68\u003c/sup\u003e, where the structural mechanism in part relies on smaller Ags hiding inside antigen-binding clefts (particularly for the CD1 system) \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, non-permissive lipids, such as long chain SM (42:2), bound by CD1a or CD1c can prevent docking of endo-reactive TCRs\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e. Here, we show that TRAV26 TCRs engage CD1d when displaying a variety of headgroup-containing lipids, over the extreme side of the A\u0026acute;-roof, without contacting the protruding headgroups. Accordingly, both the α1 and α2helixes of the A\u0026acute;-roof are heavily contacted by TRAV26-2 TCR α-chain and may form an anchor region within CD1d targeted by non-type I NKT TCRs, including the \u0026lsquo;atypical\u0026rsquo; CD1d-α-GalCer reactive NKT TCRs (\u003cem\u003eTRAV10\u0026ndash;TRAJ18\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sup\u003e) \u003csup\u003e22, 23, 24, 25, 26\u003c/sup\u003e, CD1d-benzofuran-self-lipid reactive type II NKT TCRs \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, and the murine sulfatide reactive TCRs\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, all previously structurally described CD1d interactions involve NKT TCR co-engagement of CD1d and their cognate lipid, which contrasts our novel study of TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs.\u003c/p\u003e"},{"header":"Limitations of the Study and future directions","content":"\u003cp\u003eThe TCR patterns identified among CD1d-endo reactive clones followed in vitro expansion of sorted cells, which is commonly used in studies of rare populations \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e and was necessary for us to confidently identify these cells. While it is possible this may have altered the representation of some TCRs within the population, the expansion is based on anti-CD3 stimulation and therefore should not inherently favour any particular TCRs. While this approach precludes addressing immune-function ex vivo, nonetheless, we have shown that expanded TRAV26 cells are capable of producing a range of cytokines, in particular TNF and IFNγ, implying that these cells have pro-inflammatory potential and future studies will investigate their contributions to various health and disease states. It will also be important to address the intrinsic or extrinsic regulatory mechanisms that define the activity and immune function of TRAV26, including their reliance on secondary signals such as cytokines \u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e or other receptors such as NK receptors \u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e, which can play a role in modulating activation status in a TCR-independent manner. Most importantly, our findings suggest that TRAV26 cells are highly represented within the CD1d-endo reactive population and are present as a public TCR in essentially all individuals tested. The potential significance of these observations is highlighted by an earlier study where we revealed the TRAV12-TRAJ6 type II NKT TCR motif \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, specifically reactive to small benzofuran-like molecules bound by CD1d. That TCR motif was subsequently implicated in Crohn\u0026rsquo;s disease \u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e, \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u003c/sup\u003e where the cells were named Crohn\u0026rsquo;s-associated invariant T cells (CAIT cells), which is now underpinning studies to investigate the contributions of CAIT cells and the CD1d axis to this disease.\u003c/p\u003e\u003cp\u003eSeveral candidate therapies have explored the immunomodulating potential of type I NKT cells, with ongoing trials also including CAR-type I NKT cell allogenic and adoptive therapies \u003csup\u003e\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e. The findings of this study may offer new avenues to modulate immune responses through the monomorphic protein CD1d and overcome existing limitations of current trials, that require a-GalCer co-delivery to allow type I NKT-activation \u003csup\u003e\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e\u003c/sup\u003e. Moreover, our observation that TRAV26 TCRs retain their ability to recognise the complex glycan headgroup of GD3 loaded onto CD1d, which inhibits type I NKT responses \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e, flags their potential exploration in therapies against GD3-expressing cancers. These findings further highlight the possibility of future immunomodulation agonists, antagonists or anti-TCR antibodies to selectively manipulate these public TRAV26\u003csup\u003e+\u003c/sup\u003e type II NKT cells.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cb\u003eFlow cytometry.\u003c/b\u003e Buffy coats from healthy blood donors were obtained from the Australian Red Cross Blood Service (agreement 13-04VIC-07), and all experiments were conducted in accordance with the University of Melbourne Human Research and Ethics committee guidelines (approval number 1035100). PBMCs were prepared through density gradient centrifugation using Ficoll-Paque (GE Healthcare). Cells were incubated for 10 min with Fc-receptor block (BD Pharmingen) and 5% (v/v) mouse serum, followed by CD1d-endo tetramers for 30min on ice. Where described, CD1d\u0026ndash;endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were enriched by TAME, using anti-phycoerythrin (PE) magnetic beads and LS columns (Miltenyi Biotec), and stained with secondary antibodies including: CD3ε (UCHT1, eBioscience and Becton Dickinson), CD4 (RPA-T4, BD Pharmingen), CD8α (SK1, BD Pharmingen), CD19 (HIB19, BioLegend), CD14 (MφP9, BD Pharmingen), TCRγδ (11F2, BD Pharmingen), and 7-aminoactinomycin D (7AAD) viability dye (Sigma). CD3\u003csup\u003e+\u003c/sup\u003e CD1d\u0026ndash;endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were sorted using a FACSAria (BD Biosciences). When reassessed immediately after the first-sort, purities ranged 13\u0026ndash;65%. Where described, sorted cells were then expanded for 18\u0026ndash;21 days, whereby in the first two they were exposed to plate bound anti-CD3 (10 \u0026micro;g/mL, UCHT1, BD Pharmingen) and anti-CD28 (5\u0026micro;g/mL, CD28.2, BD Pharmingen), in the presence of IL-2 (20 U/mL, Prepotech) IL-7 (50 ng/mL, eBioscience) and IL-15 (40 pg/mL), in complete RPMI-1640 supplemented with 10% (v/v) FBS (JRH Biosciences), penicillin (100 U/ml, Sigma), streptomycin (100 \u0026micro;g/ml), Glutamax (2 mM), sodium pyruvate (1 mM), nonessential amino acids (0.1 mM), HEPES buffer (15 mM, pH 7.2\u0026ndash;7.5) (all from Invitrogen, Life Technologies) and 2-mercaptoethanol (50 \u0026micro;M, Sigma). After expansion cells were re-stained with CD1d-endo tetramers alone, followed by surface antibodies and secondary CD1d-endo as well as CD1d-α-GalCer tetramer staining. These sorted and expanded CD3\u003csup\u003e+\u003c/sup\u003eCD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were then index-sorted as single cells for TCR sequencing. Data analysis was completed using FlowJo (Tree Star Inc), and graphs generated using GraphPad Prism.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLipids.\u003c/b\u003e α-GalCer C24:1 (PBS44) used for CD1d tetramers was kindly provided by P. Savage (Brigham Young University). α-GalCer C26:0 used for cellular activation assays was supplied by Alexis Biochemicals, and SM C42:2, SM C34:1, PC C42:1; sulfatide C42:2, PE C36:1, PS C36:1 PC C36:1, PC C42:2, PI C36:1, PG C36:1, LPE C18:1, LPC C18:1, pLPE C18:1 from Avanti Polar Lipids. Disialo-ganglioside GD3 C34:1 was purchased from Matreya. CD1d-ligands were dissolved in tris buffer saline (TBS) alone (pH 8) or TBS containing 0.05% v/v tyloxapol (Sigma), or buffer containing 0.5% v/v tween-20, 57 mg/ml sucrose and 7.5 mg/ml histidine, and exogenously loaded overnight into soluble biotinylated CD1d at 12-fold molar excess (except for α-GalCer - loaded at 6-fold), prior to tetramerization.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIdentification of the NKT TCRs.\u003c/b\u003e CD3\u003csup\u003e+\u003c/sup\u003eCD1d-endo tetramer\u003csup\u003e+\u003c/sup\u003e cells were single-cell sorted from CD1d-endo tetramer-enriched and culture-expanded NKT cells (as described above), and cDNA generated using 0.1% Triton X-100 (Invitrogen) and SuperScript VILO according to manufacturer\u0026rsquo;s instructions. Paired TCRα and TCRβ or TCRγ and TCRδ chain-transcripts were amplified as previously described \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. PCR products were sequenced at the AGRF facility (Australia) and analysed using IMGT \u003csup\u003e\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u003c/sup\u003e. TCR nomenclature is presented in accordance with the IMGT guidelines. Unproductive TCR gene rearrangements were excluded from analysis. The first 10 amino acids of the CDR3α of TRAV26 TCRs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb were aligned using Logomaker \u003csup\u003e\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eGeneration of stable cell lines and stimulation assay.\u003c/b\u003e TCR constructs containing the full-length TCRα and TCRβ or TCRδ and TCRγ chains separated by a 2A-cleavable linker were synthesized (Genscript) and cloned into the pMIGII plasmid. TCR-deficient SKW3.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e cells were retrovirally transduced with the TCR and a 2A-cleavable human CD3 \u003csup\u003e77\u003c/sup\u003e, plus the packaging vectors pEQ-Pam-3-E pVSV-G and using HEK293T cells as packaging cells and FUGENE 6 (Promega), as previously described \u003csup\u003e\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e\u003c/sup\u003e. The pMIGII, expression and packaging vectors were provided by Dr. Dario Vignali (St. Jude\u0026rsquo;s Research Hospital, USA), and the CD3 expression vector was provided by Prof. Stephen Turner (Monash University, Australia). CD3(GFP)\u003csup\u003ehi\u003c/sup\u003e cells were sorted and assessed for their ability to bind CD1d tetramers by flow cytometry. For Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, HEK293T cells were transiently transduced with CD3 and TCR vectors in the same manner but in the absence of packaging vectors and assessed after 48h for CD3/TCR expression and CD1d-tetramer binding by flow cytometry. C1R cells were transduced to express human CD1d or mutated versions of CD1d, akin to SKW3.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e cells, and purified using flow cytometric sorting to produce stable cells lines expressing similar surface levels of CD1d \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eActivation assays.\u003c/b\u003e For stimulation assays, TCR-expressing SKW3.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e cells were co-cultured overnight in complete RPMI (as described above), with or without C1R cells (either C1R.WT, C1R.CD1d or C1R.β2m\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e) cells, with α-GalCer C26:0 at 1 \u0026micro;g/mL, sulfatide C42:2, SM C42:2 or GD3 C34:1 at 20 \u0026micro;g/mL, or vehicle controls, and with either anti-CD1d (51.1, Biolegend), isotype control antibody (MPC-11 or MG2b-57, Biolegend) or media alone, in round-bottom 96-well plates. Activation of TCR-transduced cells was analysed by flow cytometry for CD69 upregulation using anti-CD69 (FN50, BD Pharmingen). For functional analysis of PBMCs, CD1d-endo tetramer positive or negative cells that had been FACS-sort expanded for 20 days as described above were exposed to 10 ng/mL PMA, 1 \u0026micro;g/mL Ionomicyn and 1/1000, Golgi stop (1/500, BD Pharmingen), Brefeldin A (1/1000, BD Pharmingen) and for 4h in complete media prior to assessment of intracellular cytokine production using BD Cytofix/Cytoperm kit (BD Biosciences), anti-TNF (MAb11, BD Pharmingen), anti-IFNg (4S.B3, Biolegend) and anti-IL-13 (JES10-5A2, BD Pharmingen).\u003c/p\u003e\u003cp\u003e\u003cb\u003eCD1d and NKT TCRs production and purification.\u003c/b\u003e The human CD1d sequence encoding for truncated recombinant human CD1d ectodomain harbouring a C-terminal BirA and six-histidine (GSGLNDIFEAQKIEWHEHHHHHH) affinity tags, and β2-microglobulin, both in separate pHLsec vectors, were co-transfected into GnTI\u003csup\u003e\u0026minus;/\u0026minus;\u003c/sup\u003e HEK293S for expression using polyethyleneimine as described\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e\u003c/sup\u003e. The soluble CD1d glycoprotein was purified by Ni/NTA affinity purification followed by size-exclusion chromatography using a Superdex 200 16/60 column (GE Healthcare). CD1d was enzymatically biotinylated using biotin ligase (produced in-house) and further purified by size-exclusion chromatography using a Superdex-75 16/60 gel-filtration column (GE healthcare), followed by storage at \u0026minus;\u0026thinsp;80\u0026deg;C. Biotinylated CD1d proteins carrying endogenous lipids (endo), or exogenously loaded \u003cem\u003ein vitro\u003c/em\u003e (as described in the lipids section) were tetramerised using SAV-PE or SVA-BV421 (Biolegend).\u003c/p\u003e\u003cp\u003eThe genes encoding the T26A (TRAV26-TRBV19), T14 (TRAV14-TRBV19) and T26B (TRAV26-TRBV13) TCRs after codon optimization, were synthesized (Genscript) and cloned into the expression vector pET30 (Novagen). The TCRα and TCRβ chains of the three NKT TCRs were expressed in \u003cem\u003eEscherichia coli\u003c/em\u003e strain BL21 and purified as inclusion bodies (IBs) as described\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The IBs were resuspended in the following buffer: 8 M urea, 0 mM Tris-HCl-pH 8.0, 0.5 mM Na-EDTA, 1 mM DTT. The three TCRs were refolded by dilution in a solution containing 5 M urea, 0.1 M Tris-HCl-pH 8.0, 2 mM Na-EDTA, 400 mM L-arginine-HCl, 0.5 mM oxidized glutathione, 5 mM reduced glutathione. The refolding solutions were then dialyzed against 10mM Tris pH 8.0. The NKT TCRs were purified by Diethyl aminoethyl (DEAE) anion exchange, size exclusion and HiTrap-Q anion-exchange chromatography techniques.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIn vitro\u003c/b\u003e \u003cb\u003eloading of lipids into human CD1d for crystallography and SPR.\u003c/b\u003e Lipid solutions of GD3, sulfatide and ⍺-GalCer were prepared at 1 mg/mL in 0.5% tyloxapol. Prior to lipid loading, the lipid solutions were sonicated for 30 mins and immediately transferred to a 60\u0026deg;C water bath for 1 min and left to cool at room temperature for 1 min. The lipids GD3,sulfatide were then added directly to CD1d-endo at a 3\u0026ndash;6:1 molar ratio and incubated in 10ml TBS150 (Tris buffered saline, 150mM NaCl, 10mM Tris pH 8.0) at room temperature for 15 h. The lipid-loaded CD1d were then purified by MonoQ anion-exchange chromatography (GE Healthcare). α-GalCer was loaded at a 6:1 molar ratio into the purified CD1d-GD3 binary complex and purified by MonoQ anion-exchange chromatography.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePurification of TCR-CD1d-endo complex and mass spectrometry analysis.\u003c/b\u003e The T26A, T26B or T14 TCRs were incubated with CD1d-endo for 16 hours. The mixture was then subjected to gel filtration on a Superdex 200 16/60 column (GE Healthcare) to isolate the TCR-CD1d-endo ternary complex. The \u0026lsquo;TCR trap\u0026rsquo; assay was performed as previously described with minor changes \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. The gel filtration protein fractions were subjected to Bligh and Dyer extraction, and the extracted lipids were initially analysed by shotgun nano-electrospray on a Thermo Fisher LXQ Ion Trap mass spectrometer. For the semi-quantitative, high resolution mass analysis, the lipid eluents were normalized to 20 \u0026micro;M based on the input proteins and 10 \u0026micro;l was injected into a reversed-phase HPLC system (Agilent Poroshell EC-C18 column, 1.9-micron, 3 x 50 mm) with an Agilent 6520 Accurate-Mass Q-TOF mass spectrometer. The gradient conditions were modified from a prior method (Klooster, elife, 2020): the mobile phases were (A) 2 mM ammonium formate in 90/10 methanol/water (v:v) and (B) 2 mM ammonium formate in 90/10/0.1 1-propanol/cyclohexane/water (v:v:v). The 30-minute gradients were: 0\u0026ndash;4 min of 100% A, 4\u0026ndash;13 min from 100% A to 100% B, 13\u0026ndash;18 min of 100% B, 18\u0026ndash;20 min from 100% B to 100% A, and 20\u0026ndash;30 min of 100% A.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSurface plasmon resonance (SPR) measurements and analysis.\u003c/b\u003e All the experiments were performed at 25\u0026deg;C on Biacore 3000 and T200 using HBS buffer (10 mM HEPES- HCl - pH 7.4, 150 mM NaCl). Biotinylated CD1d-endo, CD1d-sulfatide, CD1d-α-GalCer and CD1d-GD3 were coupled (~\u0026thinsp;3,000 RU) onto a research-grade SA chip and the four TCRs were applied at a flow rate of 5 \u0026micro;l/min. The first flow cell was left blank and was used as a reference for subsequent analysis. The final response was calculated by subtraction of the response of the streptavidin-coated chip alone from that of TCR-CD1d-lipid interaction. BIAevaluation Version 3.1 (Biacore AB) and Biacore T200 Evaluation Software 3.2.1 were used to fit the data to the 1:1 Langmuir binding model. GraphPad Prism 10 was used for data presentation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCrystallization, structure determination and refinement.\u003c/b\u003e The T26A NKT TCR-CD1d-endo (7 mg/ml) and the T26A NKT TCR-CD1d-GD3 (7 mg/ml) ternary complexes were both crystallized in 16\u0026ndash;24% PEG 3350, 0.1M sodium citrate, 0.1 M citrate-bis-Tris-pH 7 using the hanging-drop diffusion method at 20\u0026deg;C. The crystals were cryoprotected in 10% glycerol and flash-frozen in liquid nitrogen. Crystallographic data were collected at the MX2 beamline (Australian Synchrotron). Data were processed with the XDS software \u003csup\u003e\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u003c/sup\u003e and scaled using SCALA from the CCP4 suite of programs \u003csup\u003e\u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e\u003c/sup\u003e. The crystal structure of the T26A NKT TCR-CD1d-endo ternary complex was determined by molecular replacement method using PHASER \u003csup\u003e\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e\u003c/sup\u003e and the TCRα (Protein Data Bank accession code: 6RSY) \u003csup\u003e\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e\u003c/sup\u003e, TCRβ (PDB accession code: 5JHD) \u003csup\u003e\u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e\u003c/sup\u003e and human CD1d\u0026ndash;α-GalCer (PDB accession code: 2PO6) \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e as search models. The crystal structure of the T26A NKT TCR-CD1d-GD3 ternary complex was also solved by molecular replacement using PHASER and the T26A NKT TCR-CD1d-endo ternary complex as a search model. Both ternary complexes were refined using the Phenix refinement program \u003csup\u003e\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e\u003c/sup\u003e, and the COOT program \u003csup\u003e\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e\u003c/sup\u003e was used for macromolecular model building. The quality of the structures was validated using the Research Collaboratory for Structural Bioinformatics Protein Data Bank Data Validation and Deposition Services. All structural diagrams were created using PyMOL \u003csup\u003e\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe coordinates of the T26A NKT TCR-CD1d-SM and T26A NKT TCR-CD1d-GD3 ternary complexes were deposited in the Protein Data Bank (PDB) database under the accession codes 8SGB and 8SGM, respectively. All remaining data are available within the article and associated files and upon reasonable request from the corresponding authors. Source data are provided in this paper.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Paul Savage (Brigham Young University, UT, USA) and Spencer Williams (Bio21, University of Melbourne, Australia) for providing lipid antigens, and Dr Sidonia Eckle for providing the MAIT TCR control SKW3 line (clone AF7). We thank staff from the Flow Cytometry facility at the Peter Doherty Institute, David Price (statistician at the Doherty Institute) for \u0026nbsp;advice on data distribution display\u003cem\u003e\u0026nbsp;and staff at the MX2 beamline at the Australian Synchrotron and\u0026nbsp;\u003c/em\u003eMacromolecular Crystallization Platform \u003cem\u003e\u003csup\u003e88\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e.\u0026nbsp;\u003c/em\u003eThis work was supported by a University of Melbourne Early Career Researcher grant (C. F. A.), the National Health and Medical Research Council of Australia (NHMRC: 1145373, 1113293, 200891, 31106741, 2008913 and 2029256), the Australian Research Council (ARC: DP170104386, DP210103064\u0026nbsp;and\u0026nbsp;DP220102402). D. G. P. was supported by a CSL Centenary Fellowship and is now supported by a Sylvia \u0026amp; Charles Viertel Fellowship; D. I. G. was supported by an NHMRC Senior Principal Research Fellowship (1117766) and subsequently, an NHMRC Investigator Award (2008913).\u0026nbsp;J. R. is supported by an NMHRC Investigator Award (2008981). D. B. M. is supported by the NIH (AR 048632, AI 049313). D.B.M and J.R. are supported by a Welcome Trust Discovery Award.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK. C. Y. P. and C. M. H. are joint co-first authors who along with, T. Y. C., R. L., E. B., C. V. N-R., C. S., S. J. J. R, C. M., A.P.U. and C. F. A. contributed to data generation, data analysis and/or paper editing. D. B. M., J. R., D. I. G, D. G. P., J. L. N. and C. F. A. contributed to project conceptualisation, funding acquisition, data interpretation, paper reviewing and editing. K. C. Y. P. and C. M. H., J. L. N. and C. F. A. co-wrote the initial draft. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD. I. G and C. F. A hold two patents on CD1-targetting for immune modulation.\u003cstrong\u003e\u003c/strong\u003e\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGodfrey DI, MacDonald HR, Kronenberg M, Smyth MJ (2004) Van Kaer, L. NKT cells: what's in a name? Nat Rev Immunol 4:231\u0026ndash;237\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGodfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB (2015) The burgeoning family of unconventional T cells. Nat Immunol 16:1114\u0026ndash;1123\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCao TP et al (2024) A structural perspective of how T cell receptors recognize the CD1 family of lipid antigen-presenting molecules. J Biol Chem 300:107511\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCardell S et al (1995) CD1-restricted CD4\u0026thinsp;+\u0026thinsp;T cells in major histocompatibility complex class II-deficient mice. J Exp Med 182:993\u0026ndash;1004\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChiu YH et al (1999) Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J Exp Med 189:103\u0026ndash;110\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBehar SM, Podrebarac TA, Roy CJ, Wang CR, Brenner MB (1999) Diverse TCRs recognize murine CD1. J Immunol 162:161\u0026ndash;167\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlmeida CF et al (2021) Benzofuran sulfonates and small self-lipid antigens activate type II NKT cells via CD1d. Proc Natl Acad Sci U S A 118:e2104420118\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSingh AK, Tripathi P, Cardell SL (2018) Type II NKT Cells: An Elusive Population With Immunoregulatory Properties. Front Immunol 9:1969\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDhodapkar MV, Kumar V (2017) Type II NKT Cells and Their Emerging Role in Health and Disease. J Immunol 198:1015\u0026ndash;1021\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNair S et al (2015) Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. Blood 125:1256\u0026ndash;1271\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou D et al (2004) Lysosomal glycosphingolipid recognition by NKT cells. 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Acta Crystallogr D 66:486\u0026ndash;501\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePymol The PyMOL Molecular Graphics System, Version 2.0 Schr\u0026ouml;dinger, LLC\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAragao D et al (2018) MX2: a high-flux undulator microfocus beamline serving both the chemical and macromolecular crystallography communities at the Australian Synchrotron. J Synchrotron Radiat 25:885\u0026ndash;891\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7004764/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7004764/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMost studies of CD1d-restricted Natural killer T cells (NKT) have focussed on type I \u003cem\u003eTRAV10-TRAJ18\u003c/em\u003e\u003csup\u003e+\u003c/sup\u003e NKT cells that recognise the glycolipid a-GalCer. Our understanding of type II NKT cells, their TCR gene usage and ligand diversity remains unclear. Here, using CD1d tetramers carrying diverse endogenous lipids (CD1d-endo), we identified public human TRAV26\u003csup\u003e+\u003c/sup\u003e type II NKT TCRs present in all individuals, with many expressing a conserved \u003cem\u003eTRAV26-2-TRAJ48\u003c/em\u003e TCRa chain. Cellular, molecular and lipidomic analyses showed that TRAV26\u003csup\u003e+\u003c/sup\u003e TCRs bound with similar affinities to CD1d loaded with diverse lipids, suggesting lipid-independent binding. Crystal structures of TRAV26\u003csup\u003e+\u003c/sup\u003e TCR-CD1d complexes showed these TCRs bound solely to the A'-roof of CD1d, distant from the protruding lipid. Collectively we have uncovered a population of public lipid-independent TRAV26\u003csup\u003e+\u003c/sup\u003e type II NKT cells, suggesting a potential role in diseases where aberrant CD1d expression occurs.\u003c/p\u003e","manuscriptTitle":"A conserved human population of TRAV26+ type II Natural Killer T cells solely recognise CD1d","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-05 09:32:19","doi":"10.21203/rs.3.rs-7004764/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0af4ad47-159e-49dd-9924-7f4def651fd1","owner":[],"postedDate":"December 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":59140537,"name":"Biological sciences/Immunology/Lymphocytes/T cells/NKT cells"},{"id":59140538,"name":"Biological sciences/Immunology/Antigen processing and presentation/Cellular immunity"}],"tags":[],"updatedAt":"2025-12-22T12:50:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-05 09:32:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7004764","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7004764","identity":"rs-7004764","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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