T cell receptor triggering by force

Antigen recognition through the interaction between the T cell receptor (TCR) and peptide presented by major histocompatibility complex (pMHC) is the first step in T cell-mediated immune responses. How this interaction triggers TCR signalling that leads to T cell activation is still unclear. Taking into account the mechanical stress exerted on the pMHC–TCR interaction at the dynamic interface between T cells and antigen presenting cells (APCs), we propose the so-called receptor deformation model of TCR triggering. In this model, TCR conformational change induced by mechanical forces initiates TCR signalling. The receptor deformation model, for the first time, explains all three aspects of the TCR triggering puzzle: mechanism, specificity, and sensitivity.