T cell transcriptional landscapes are shaped by TCR sequence similarity

ABSTRACT T cells exhibit high heterogeneity in both their gene expression profiles and antigen specificities, but the precise relationship between these two features remains largely unknown. Utilizing a large-scale single-cell immune-profiling dataset that includes both T cell receptor (TCR) sequences and gene expression profiles of individual cells, we systematically investigated how the transcriptional profiles of T cells are linked to their TCR sequence similarity. We observed that T cells sharing the same clonotype often belong to the same cell type, and that gene expression similarity among T cells correlates with TCR sequence similarity. Furthermore, we identified features such as clonality, VJ gene usage, sequence motifs, and amino acid preferences that are distinctly associated with specific T cell subtypes. These findings suggest that T cell transcriptional landscapes are broadly shared and influenced by TCR sequence similarity.