Title Antigen-specific TCR-pMHC Catch Bond Enables Force to Trigger T cell Signaling
Speaker Dr.Cheng Zhu，Georgia Institute of Technology
Time December 19, 2012, 10:00 AM
Venue Room 204, SIBCB Building B
Host PI Prof. Chenqi Xu
Abstract Recognition of peptide bound to the major histocompatibility complex (pMHC) molecule by the T cell receptor (TCR) determines T-cell selection, development, differentiation, fate and function. Force may apply to TCR–pMHC bonds, thereby triggering T-cell signaling. However, it is unclear how force alters the stability of TCR–pMHC bonds and how such alteration impacts TCR triggering. Here we used a single-bond mechanical assay with concurrent Ca2+ imaging to elucidate how force regulates TCR dissociation from and response to pMHCs with varying potencies. Force elicited catch bonds of TCR with agonist pMHCs, but not weak ligands, at ≤10pN. Beyond this force the catch bonds transitioned to slip bonds. The peptide-specific catch-slip bonds enabled force to reverse the negative correlation of peptide potency with zero-force stability of TCR–pMHC bonds and to expand the dynamic range of their lifetimes. Calcium signals were triggered after ~1 min of repetitive 10-pN forces on multiple TCRs to prolong their ligand engagement. Our data support a model where T cell triggering requires frequent application of optimal levels of force to TCRs via agonist pMHCs in a narrow time window to rapidly accumulate activating signal intermediates generated by individual force application.
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