Formation of catch and slip bonds at immune cell interfaces

Mechanotransduction during immune recognition via cell-cell contact is essential for enhancing specificity of immune responses. Formation of catch bonds between T cell receptors (TCRs) and agonist peptide-MHC complexes (pMHCs) displayed on antigen presenting cells is considered a key mechanism. However, recent studies indicate an absence of physical catch in the bound complex despite its increased stability, questioning the mechanistic origin of catch and slip bonds. Here we propose that membrane topography and receptor mobility may interplay to provide an alternative source of mechanical forces and induce both catch and slip regimes in the force-stability relationship. Using a simple stochastic model of TCR-pMHC interaction under geometrical constraints, we show that catch-bond behavior has a sharp dependence on complex size and membrane stiffness, suggesting an extrinsic mechanism for sensitive ligand discrimination agnostic of structural details. Interestingly, our model predicts that mobility-induced catch bonds can only maintain high-stability states under non-equilibrium conditions. Our work offers a new perspective for understanding biological recognition, which stresses the importance of considering physical constraints that a cell may exploit to sharpen its functional responses.