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Nature. 2002 Aug 1;418(6897):552-6.

Two-step binding mechanism for T-cell receptor recognition of peptide MHC.

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1
Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, B221 Beckman Center, Stanford, California 94305, USA.

Abstract

T cells probe a diverse milieu of peptides presented by molecules of the major histocompatibility complex (MHC) by using the T-cell receptor (TCR) to scan these ligands with high sensitivity and specificity. Here we describe a physical basis for this scanning process by studying the residues involved in both the initial association and the stable binding of TCR to peptide-MHC, using the well-characterized TCR and peptide-MHC pair of 2B4 and MCC-IE(k) (moth cytochrome c, residues 88 103). We show that MHC contacts dictate the initial association, guiding TCR docking in a way that is mainly independent of the peptide. Subsequently, MCC-IE(k) peptide contacts dominate stabilization, imparting specificity and influencing T-cell activation by modulating the duration of binding. This functional subdivision of the peptide-MHC ligand suggests that a two-step process for TCR recognition facilitates the efficient scanning of diverse peptide-MHC complexes on the surface of cells and also makes TCRs inherently crossreactive towards different peptides bound by the same MHC.

PMID:
12152083
DOI:
10.1038/nature00920
[Indexed for MEDLINE]
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