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Significance T lymphocytes use their T cell receptors (TCRs) to discriminate between similar peptide-MHC (pMHC) antigens. The mechanisms employed to achieve this discrimination are debated. The TCR–pMHC interaction is subjected to forces, and recent work in live T cells has suggested that force paradoxically increases TCR–pMHC bond lifetimes for activating peptides, forming so-called “catch bonds,” facilitating discrimination from nonactivating peptides. A question is whether this behavior is intrinsic to the TCR–pMHC bond or a cellular response. We measured TCR–pMHC lifetimes under force in a cell-free system: lifetimes correlated well with activation potency of the TCR–pMHC bonds, while no catch bonds were observed. However, a minimum encounter duration is necessary for bond formation, which could increase specificity.

TCR–pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration before binding