The αβTCR mechanosensor exploits dynamic ectodomain allostery to optimize its ligand recognition site

αβT cell receptors (TCRs) recognize antigenic peptide bound to major histocompatibility complex (pMHC) molecules with exquisite sensitivity. An emerging concept is that αβTCR functions as a mechanosensor whereby the complex between its ligand-binding TCRαβ heterodimer and pMHC increases the bond lifetime under physiological-level force, the so-called catch bond. This study reveals the physical mechanism for catch bond behavior. Multiple layers of control are identified, including the dynamics of interfacial contacts, and the motion and geometry of the four subdomains of TCRαβ, all of which are influenced by the load applied to the TCRαβ-pMHC complex. These findings shall contribute to understanding the TCR mechanobiology and shall assist with design of future TCR-based immunotherapies.