The T cell receptor sequence influences the likelihood of T cell memory formation
Year: 2024
Type: article
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 αβTCR 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 CDR2α, that promotes positive selection in the thymus as well as transition from naïve 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.
Source: Cell Reports
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: Life Sciences Research Foundation, Mark Foundation For Cancer Research, Cancer Research UK, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1038091005, G1227577725, G1330203626, Defining the influence of RA genetic susceptibility factors on T cell antigen specificity and functional state, G1624947793, G166548656, G1837346394, G1972444143, G3608066283, Metabolic factors that control the spectrum of human tuberculosis, G442117160, G4698129410, G478142150, Repertoire-scale T cell antigen identification via peptide-MHC lentivirus display, G636133789, G638946321, G6556997795, G694218531, G707340384, G9000002510, G9000005946, G9000007836, G9000083956, G9000086738, G9000125632, G9000126733, G9000153912, G9000164145, G9000183381, G9000212843, G9000254646, G9000323727, Training in Bioinformatics and Integrative Genomics, Integrative modelling of single-cell data to elucidate the genetic architecture of complex disease, G932915660
OpenAlex ID: W4405848800