T-cell antigen recognition: catch-as-catch-can or catch-22?

Johannes B Huppa, Gerhard J Schütz

The EMBO journal 2023 Apr 03

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T-cell antigen recognition is invariably affected by tensile forces as they are exerted on T-cell antigen receptors (TCRs) transiently binding antigenic peptide/MHC complexes. In this issue of The EMBO Journal, Pettmann and colleagues promote the concept that forces reduce the lifetime of more stable stimulatory TCR-pMHC interactions to a larger extent than that of less stable non-stimulatory TCR-pMHC interactions. The authors argue that forces impede rather than boost T-cell antigen discrimination, which is promoted by force-shielding within the immunological synapse through cell adhesion via CD2/CD58 and LFA-1/ICAM-1. © 2023 The Authors.