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Abstract
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 Ca(2+) 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 Ca(2+) levels require early and rapid accumulation of bond lifetimes,
whereas short-lived bonds that slow early accumulation of lifetimes correspond to
low Ca(2+) responses. Our data support a model in which 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.