Mechanosensing drives acuity of αβ T-cell recognition

AUTHORS

Feng Y. , Brazin K.N. , Kobayashi E. , Mallis R.J. , Reinherz E.L. , Lang M.J. . PNAS. 2017 ; 114(39). E8204-E8213

PMID: 28811364[PubMed].
PMCID: PMC5625899.

ABSTRACT

T-lymphocyte activation during immune surveillance begins with recognition by its $α β$ T-cell receptor (TCR) of a peptide ligand bound to an MHC molecule (pMHC) on infected or otherwise altered cells. Using optical traps, we show that activation is fostered at the single-molecule level through synergy between external load on the TCR–pMHC bond and internal, sustained stepping via motor-dependent transport. Chemical thresholds in the absence of load require much higher pMHC density than observed physiologically. With load, however, T lymphocytes can be reliably activated with $\sim$ 10 pN per TCR molecule, mimicking native shear motions involving a mere two pMHCs at the interaction surface. Initial TCR triggering sensitivity results from synergistic mechanosensing rather than previously postulated serial engagement.