Mechanical forces amplify TCR mechanotransduction in T cell activation and function

, mechanical cues that regulate their biology have been largely underappreciated. This review highlights the contributions of mechanical force to several receptor-ligand interactions critical to T cell function, with central focus on the TCR-peptide-loaded major histocompatibility complex (pMHC). We then emphasize the role of mechanical forces in (i) allosteric strengthening of the TCR-pMHC interaction in amplifying ligand discrimination during T cell antigen recognition prior to activation and (ii) T cell interactions with the extracellular matrix. We then describe approaches to design eTCRs, CARs, and biomaterials to exploit TCR mechanosensitivity in order to potentiate T cell manufacturing and function in adoptive T cell immunotherapy.