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Engagement of the TCR by antigenic peptides presented by the MHC activates specific T cells to control infections. Recent theoretical considerations have suggested that mechanical forces acting on the TCR may be important for receptor triggering. In this study, we directly tested the hypothesis that physical forces acting on the TCR can initiate signaling in T cells by micromanipulation of individual T cells bound to artificial APCs expressing engineered TCR ligands. We find that mechanical forces acting on T cells bound to APCs via the TCR complex but not other surface receptors can initiate signaling in T cells in an Src kinase-dependent fashion. Our data indicate that T cells are mechanically sensitive when coupled to APCs by the TCR and indicates that the TCR may act as a mechanosensor. Our data provide new insight into TCR function.

Cutting Edge: Mechanical Forces Acting on T Cells Immobilized via the TCR Complex Can Trigger TCR Signaling