Mechanical Cues for T Cell Activation: Role of Piezo1 Mechanosensors

Abstract

T cells are activated in response to the recognition of antigenic peptides on major histocompatibility complex molecules (pMHC) by the T cell receptors (TCR) and induction of downstream signaling. The strength of interaction between specific TCR with pMHC is a key defining factor for optimal T cell activation. But a number of studies have also suggested a crucial involvement of mechanical cues within the immunological synapse. However, a dedicated mechanosensor molecule that senses and transduces the mechanical cues to optimize TCR activation was, until very recently, not known. The putative candidates included the TCR itself as well as the integrins within the immunological synapse. Recently, the Piezo family of proteins was discovered as professional mechanosensors implicated in a number of physiological processes. One of the two Piezo family members, Piezo1, is expressed in human T cells. Recent data suggest that Piezo1 functions as a professional mechanotransducer at the immunological synapse during TCR-pMHC interaction, and thus play a crucial role in human T cell activation. Thus, the domain of T cell activation has gathered a new mechanoregulatory dimension, which should incite further studies for detailed elucidation of the mechanistic underpinnings and its translational implications.