Seeing the change: TCR binds pMHC with an ‘induced-fit’

Abstract

At the molecular level, T-cell recognition of the peptide–MHC (pMHC) on antigen-presenting cells (APCs) is orchestrated by several protein–protein interactions on the surfaces of both cells. Among them, the interaction of T-cell receptor (TCR) on the surface of T cells with its ligand, pMHC, is characterized by low-affinity, slow kinetics and a high degree of cross-reactivity. Based on only one available bound and unbound complex crystal structure of TCR–pMHC (2C TCR with H-2Kb), with some thermodynamic analysis (both class I- and class II-restricted TCRs), and one case of NMR structural analysis (D10 TCR), ‘induced fit’ or ‘local conformational readjustment’ has been proposed for the interaction between TCR and pMHC. Reiser et al. [ 1. Reiser J.B. et al. A T-cell receptor CDR3β loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide–MHC class I complex. Immunity. 2002; 16: 345-354 Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar ] now provide new evidence that local conformational readjustment does occur in the TCR–pMHC interface, upon binding of the TCR with pMHC. The authors even suggest calling this readjustment ‘conformational change’ to fit the binding.