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

Laurent Limozin (1) , Marcus Bridge (2) , Pierre Bongrand (1) , Omer Dushek (3) , Philip Anton van Der Merwe (2) , Philippe Robert (1)

1 LAI - Adhésion et Inflammation
2 Sir William Dunn School of Pathology [Oxford]
3 Sir William Dunn Pathology School

The TCR-pMHC interaction is the only antigen specific interaction during T lymphocyte activation. Recent work suggests that formation of catch bonds is characteristic of activating TCR-pMHC interactions. However, whether this binding behavior is an intrinsic feature of the molecular bond, or a consequence of more complex multimolecular or cellular responses, remains unclear. We used a laminar flow chamber to measure, firstly, 2D TCR-pMHC dissociation kinetics of peptides of various activating potency in a cell-free system in the force range (6-15pN) previously associated with catch-slip transitions and, secondly, 2D TCR-pMHC association kinetics, for which the method is well-suited. We did not observe catch bonds in dissociation, and the off-rate measured in the 6-15pN range correlated well with activation potency, suggesting that formation of catch bonds is not an intrinsic feature of the TCR-pMHC interaction. The association kinetics were better explained by a model with a minimal encounter duration rather than a standard on-rate constant, suggesting that membrane fluidity and dynamics may strongly influence bond formation.

Keywords: TCR; kinetics; force; association

Domains: Biological Physics [physics.bio-ph]

Laurent Limozin, Marcus Bridge, Pierre Bongrand, Omer Dushek, Philip Anton van Der Merwe, et al.. TCR-pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration before binding. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (34), pp.16943-16948. ⟨10.1073/pnas.1902141116⟩. ⟨hal-02407675⟩