αβ T Cell Receptor Mechanosensing Forces out Serial Engagement

Yinnian Feng, Ellis L. Reinherz, Matthew J. Lang

The αβ TCR is a mechanosensor whose force-dependent structural transition and allostery regulate peptide discrimination and pMHC bond lifetime. Application of mechanical force on the TCR during ligand recognition promotes its molecular translocation and initiates T cell immunological synapse formation. Synergy of external (cell motility based) and internal (cytoskeletal motor based) forces supports a nonequilibrium (energized) model for T cell activation through reconfiguration of the αβ TCR complex at a critical force threshold.
A digital mechanosensing mechanism defines physicochemical thresholds with significant implications for CTL-based vaccines and immunotherapies. That knowledge affords new insights relative to earlier αβ TCR activation models based on equilibrium processes.

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