Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.

ABSTRACT: αβT cells protect vertebrates against many diseases, optimizing surveillance using mechanical force to distinguish between pathophysiologic cellular alterations and normal self-constituents. The multi-subunit αβT-cell receptor (TCR) operates outside of thermal equilibrium, harvesting energy via physical forces generated by T-cell motility and actin-myosin machinery. When a peptide-bound major histocompatibility complex molecule (pMHC) on an antigen presenting cell is ligated, the αβTCR on the T cell leverages force to form a catch bond, prolonging bond lifetime, and enhancing antigen discrimination. Under load, the αβTCR undergoes reversible structural transitions involving partial unfolding of its clonotypic immunoglobulin-like (Ig) domains and coupled rearrangements of associated CD3 sub

SUBMITTER: Mallis RJ 

PROVIDER: S-EPMC11744257 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature