Mechanoimmunology of T‐Cell Activation

ABSTRACT T‐cell activation, a pivotal process in the adaptive immune response, is initiated when the T cell receptor (TCR) recognises and binds to antigenic peptide‐major histocompatibility complex (pMHC) molecules on the cell membrane. Emerging evidence indicates that mechanical cues regulate T‐cell activation by modulating TCR signalling and mechanotransduction pathways, although the precise underlying mechanisms remain elusive. This review highlights recent findings suggesting that the TCR functions as a mechanosensor, capable of sensing and transmitting mechanical forces through conformational changes. Key steps in T‐cell mechanotransduction are discussed, including the roles of the cytoskeleton, mechanosensitive channels such as Piezo 1 and microvilli in facilitating activation. Additionally, we analyse the mechanical responses of chimeric antigen receptor T cells. Understanding the mechanobiological mechanisms underlying T‐cell activation offers novel insights and potential strategies for advancing immunotherapies and treating immune‐related disorders.