WASP facilitates tumor mechanosensitivity in T lymphocytes

Author:

Mandal SrishtiORCID,Melo Mariane,Gordiichuk PavloORCID,Acharya SayantiORCID,Poh Yeh-ChuinORCID,Li Na,Aung AereasORCID,Dane Eric L.,Irvine Darrell J.,Kumari SudhaORCID

Abstract

AbstractCytotoxic T lymphocytes (CTLs) carry out immunosurveillance by scanning target cells of diverse physical properties for the presence of antigens. While the recognition of cognate antigen by the T cell receptor is the primary signal for CTL activation, it has become increasingly clear that the mechanical stiffness of target cells plays an important role in antigen-triggered T cell responses. However, the molecular machinery within CTLs that transduces the mechanical information of tumor cells remains unclear. We find that CTL’s mechanosensitive ability requires the activity of the actin-organizing protein Wiskott-Aldrich Syndrome Protein (WASP). WASP activation is modulated by the mechanical properties of antigen-presenting contexts across a wide range of target cell stiffnesses and activated WASP then mediates mechanosensitive activation of early TCR signaling markers in the CTL. Our results provide a molecular link between antigen mechanosensing and CTL immune response and suggest that CTL-intrinsic cytoskeletal organizing principles enable the processing of mechanical information from diverse target cells.

Publisher

Cold Spring Harbor Laboratory

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