The Energetic Landscape of Catch Bonds in TCR Interfaces

Abstract Recognition of peptide/MHC complexes by αβ TCRs has traditionally been viewed through the lens of conventional receptor–ligand theory. Recent work, however, has shown that TCR recognition and T cell signaling can be profoundly influenced and tuned by mechanical forces. One outcome of applied force is the catch bond, where TCR dissociation rates decrease (half-lives increase) when limited force is applied. Although catch bond behavior is believed to be widespread in biology, its counterintuitive nature coupled with the difficulties of describing mechanisms at the structural level have resulted in considerable mystique. In this review, we demonstrate that viewing catch bonds through the lens of energy landscapes, barriers, and the ensuing reaction rates can help demystify catch bonding and provide a foundation on which atomic-level TCR catch bond mechanisms can be built.