Accumulation of Dynamic Catch Bonds between TCR and Agonist Peptide-MHC Triggers T Cell Signaling

Abstract

Summary TCR–pMHC interactions initiate adaptive immune responses, but the mechanism of how such interactions under force induce T-cell signaling is unclear. We show that force prolongs lifetimes of single TCR–pMHC bonds for agonists (catch bonds) but shortens those for antagonists (slip bonds). Both magnitude and duration of force are important as the highest Ca2+ responses were induced by 10 pN via both pMHC catch bonds whose lifetime peaks at this force and anti-TCR slip bonds whose maximum lifetime occurs at 0 pN. High Ca2+ levels require early and rapid accumulation of bond lifetimes whereas short-lived bonds that slow early accumulation of lifetimes correspond to low Ca2+ responses. Our data support a model where force on the TCR induces signaling events depending on its magnitude, duration, frequency, and timing, such that agonists form catch bonds that trigger the T cell digitally, whereas antagonists form slip bonds that fail to activate.