Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling

Cell. 2014 Apr 10;157(2):357-368. doi: 10.1016/j.cell.2014.02.053.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Presenting Cells
  • Calcium / metabolism
  • Erythrocytes / metabolism
  • Humans
  • Major Histocompatibility Complex
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / metabolism*


  • Receptors, Antigen, T-Cell
  • Calcium