HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design | 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 HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design Sonja Buschow, Amy Kessler, Wouter Doff, Roel Pieterman, Karel Bezstarosti, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4384370/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jan, 2025 Read the published version in npj Vaccines → Version 1 posted 5 You are reading this latest preprint version Abstract Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design. Biological sciences/Immunology/Antigen processing and presentation/Antigen-presenting cells Biological sciences/Immunology/Infectious diseases/Hepatitis/Viral hepatitis/Hepatitis B Major histocompatibility complex (MHC) peptide vaccination cross-presentation HLA ligandome Hepatitis B Immunopeptidomics Full Text Additional Declarations Yes there is potential Competing Interest. SB and DJ are listed as inventors on a patent application related to the work in this manuscripts on novel long peptide antigens for treatment of hepatitis B related disease, filed by ISA pharmaceuticals B.V.. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest. Supplementary Files SupplementaryFile1.xlsx Supplementaryfiguresandmethods.pdf Dataset 1 Cite Share Download PDF Status: Published Journal Publication published 18 Jan, 2025 Read the published version in npj Vaccines → Version 1 posted Unknown event 24 May, 2024 Editorial decision: Reject before peer review 17 May, 2024 Editor assigned by journal 09 May, 2024 Submission checks completed at journal 08 May, 2024 First submitted to journal 07 May, 2024 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. We do this by developing innovative software and high quality services for the global research community. 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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-4384370","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":303800933,"identity":"99b8b4cf-d78e-4009-adfd-52004a805805","order_by":0,"name":"Sonja 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