TCR Binding to Peptide-MHC Stabilizes a Flexible Recognition Interface
- 1 March 1999
- journal article
- Published by Elsevier BV in Immunity
- Vol. 10 (3), 357-365
- https://doi.org/10.1016/s1074-7613(00)80035-7
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.Keywords
This publication has 48 references indexed in Scilit:
- T Cell Receptor and Coreceptor CD8αα Bind Peptide-MHC Independently and with Distinct KineticsImmunity, 1999
- HUMAN CYTOTOXIC T LYMPHOCYTE RESPONSES TO EPSTEIN-BARR VIRUS INFECTIONAnnual Review of Immunology, 1997
- ESCAPE OF HUMAN IMMUNODEFICIENCY VIRUS FROM IMMUNE CONTROLAnnual Review of Immunology, 1997
- Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug designCell Chemical Biology, 1996
- Crystal Structure of the Complex of the Variable Domain of Antibody D1.3 and Turkey Egg White Lysozyme: A Novel Conformational Change in Antibody CDR-L3 Selects for AntigenJournal of Molecular Biology, 1996
- Transient intercellular adhesion: the importance of weak protein-protein interactionsTrends in Biochemical Sciences, 1994
- Human Cell-Adhesion Molecule CD2 Binds CD58 (LFA-3) with a Very Low Affinity and an Extremely Fast Dissociation Rate but Does Not Bind CD48 or CD59Biochemistry, 1994
- T cell receptor interaction with peptide/major histocompatibility complex (MHC) and superantigen/MHC ligands is dominated by antigen.The Journal of Experimental Medicine, 1993
- Expression of T Cell Antigen Receptor Heterodimers in a Lipid-Linked FormScience, 1990
- The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptidesCell, 1986