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.