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

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.

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Publication Details

Journal
Cell Reports
Published
2024-12-27
DOI
https://doi.org/10.1016/j.celrep.2024.115098
Citations
7
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
1.68

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article

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

Michael E. Birnbaum, Ayano C. Kohlgruber, Stephen J. Elledge, Laurie Rumker et al.
7 citations
Cell Reports
Immune Cell Function and Interaction
1.68
article

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

Michael E. Birnbaum, Ayano C. Kohlgruber, Stephen J. Elledge, Laurie Rumker, Nouran S. Abdelfattah, Kaitlyn A. Lagattuta, Aparna Nathan, Soumya Raychaudhuri
article en
7 citations

Abstract

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.

Cell ReportsVol. 44(1)
Brigham and Women's Hospital (US), Boston Children's Hospital (US), Howard Hughes Medical Institute (US), Ragon Institute of MGH, MIT and Harvard (US), Massachusetts Institute of Technology (US)
Life Sciences Research Foundation, Cancer Research UK, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 15%
Immune Cell Function and Interaction
1.68
DOIOpen Access PDFOpenAlex
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