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T-cell receptor sequences correlate with and predict gene expression levels in T cells

Wang, H.; Ji, Z.

2025-04-12 bioinformatics
10.1101/2023.11.27.568912 bioRxiv
Show 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.

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