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Structure of anti-TCRvbeta6-5 antibody in complex with the cognate TCR
Structural highlights
Publication Abstract from PubMedClonotypic alphabeta T cell responses to cargoes presented by major histocompatibility complex (MHC), MR1, or CD1 proteins underpin adaptive immunity. Those responses are mostly mediated by complementarity-determining region 3 motifs created by quasi-random T cell receptor (TCR) gene rearrangements, with diversity being highest for TCRgammadelta. Nonetheless, TCRgammadelta also displays nonclonotypic innate responsiveness following engagement of germline-encoded Vgamma-specific residues by butyrophilin (BTN) or BTN-like (BTNL) proteins that uniquely mediate gammadelta T cell subset selection. We now report that nonclonotypic TCR engagement likewise induces distinct phenotypes in TCRalphabeta(+) cells. Specifically, antibodies to germline-encoded human TCRVbeta motifs consistently activated naive or memory T cells toward core states distinct from those induced by anti-CD3 or superantigens and from others commonly reported. Those states combined selective proliferation and effector function with activation-induced inhibitory receptors and memory differentiation. Thus, nonclonotypic TCRVbeta targeting broadens our perspectives on human T cell response modes and might offer ways to induce clinically beneficial phenotypes in defined T cell subsets. Innate TCRbeta-chain engagement drives human T cells toward distinct memory-like effector phenotypes with immunotherapeutic potentials.,Vantourout P, Eum J, Conde Poole M, Hayday TS, Laing AG, Hussain K, Nuamah R, Kannambath S, Moisan J, Stoop A, Battaglia S, Servattalab R, Hsu J, Bayliffe A, Katragadda M, Hayday AC Sci Adv. 2023 Dec 8;9(49):eadj6174. doi: 10.1126/sciadv.adj6174. Epub 2023 Dec 6. PMID:38055824[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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