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

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

Summary: The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual’s immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell f...

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Main Authors: Kaitlyn A. Lagattuta, Ayano C. Kohlgruber, Nouran S. Abdelfattah, Aparna Nathan, Laurie Rumker, Michael E. Birnbaum, Stephen J. Elledge, Soumya Raychaudhuri
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
Subjects:
CP: Immunology
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724014499
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Summary:Summary: The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual’s immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells. We find that hydrophobic complementarity-determining region (CDR)3 residues promote regulatory T cell fates in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features that promote the T cell transition from naive to memory. We quantify the extent of these features through our TCR scoring function “TCR-mem.” Using TCR transduction experiments, we demonstrate that increased TCR-mem promotes T cell activation, even among T cells that recognize the same antigen. Our results reveal a common set of TCR sequence features that enable T cell activation and immunological memory.
ISSN:2211-1247

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