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

• Published in: Cell Vol. 157; no. 2; pp. 357 - 368
• Main Authors: Liu, Baoyu, Chen, Wei, Evavold, Brian D, Zhu, Cheng
• Format: Journal Article
• Language: English
• Published: United States 10-04-2014
• Subjects: 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
• ISSN: 0092-8674; 1097-4172
• 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.