The T cell receptor sequence influences the likelihood of T cell memory formation

Lagattuta, K. A.; Nathan, A.; Rumker, L.; Birnbaum, M. E.; Raychaudhuri, S.

doi:10.1101/2023.07.20.549939

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bioRxiv · 10.1101/2023.07.20.549939

The T cell receptor sequence influences the likelihood of T cell memory formation

Lagattuta, K. A.·Nathan, A.·Rumker, L.·Birnbaum, M. E.·Raychaudhuri, S.

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Abstract

T cell differentiation depends on activation through the T cell receptor (TCR), whose amino acid sequence varies cell to cell. Particular TCR amino acid sequences nearly guarantee Mucosal-Associated Invariant T (MAIT) and Natural Killer T (NKT) cell fates. To comprehensively define how TCR amino acids affects all T cell fates, we analyze the paired {beta}TCR sequence and transcriptome of 819,772 single cells. We find that hydrophobic CDR3 residues promote regulatory T cell transcriptional states in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features, concentrated in CDR2, that promotes positive selection in the thymus as well as transition from naive to memory in the periphery. Even among T cells that recognize the same antigen, these TCR sequence features help to explain which T cells form immunological memory, which is essential for effective pathogen response.

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Lagattuta, K. A., Nathan, A., Rumker, L., Birnbaum, M. E., Raychaudhuri, S.. 2023-07-23. The T cell receptor sequence influences the likelihood of T cell memory formation. https://doi.org/10.1101/2023.07.20.549939

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