Format

Send to

Choose Destination
Immunity. 1999 Mar;10(3):357-65.

TCR binding to peptide-MHC stabilizes a flexible recognition interface.

Author information

1
Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract

The binding of TCRs to their peptide-MHC ligands is characterized by a low affinity, slow kinetics, and a high degree of cross-reactivity. Here, we report the results of a kinetic and thermodynamic analysis of two TCRs binding to their peptide-MHC ligands, which reveal two striking features. First, significant activation energy barriers must be overcome during both association and dissociation, suggesting that conformational adjustments are required. Second, the low affinity of binding is a consequence of highly unfavorable entropic effects, indicative of a substantial reduction in disorder upon binding. This is evidence that the TCR and/or peptide-MHC have flexible binding surfaces that are stabilized upon binding. Such conformational flexibility, which may also be a feature of primary antibodies, is likely to contribute to cross-reactivity in antigen recognition.

PMID:
10204491
DOI:
10.1016/s1074-7613(00)80035-7
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center