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Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8844-9.

Distinct recognition by two subsets of T cells of an MHC class II-peptide complex.

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  • 1Department of Pathology and Immunology, and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

We examine here the nature of the differential recognition by CD4+ T cells of a single peptide from hen-egg white lysozyme (HEL) presented by I-A(k) class II MHC molecules. Two subsets of T cells (called A and B) interact with the same peptide, each in unique ways that reflect the nature of the complex of peptide and MHC. We show that the A and B set of T cells can be distinguished by their functional interaction with the three T cell receptor (TCR) contact residues of the bound peptide. The dominant peptide of HEL selected from processing is bound in a single register where a critical TCR contact residue is situated about the middle of the core segment of the peptide: all T cells establish functional contact with it. Three sets of T cells, however, can be distinguished by their differential recognition of two TCR contacts situated at the amino and carboxyl sides of the central TCR contact residue. Type A T cells, the conventional cells that see the peptide after processing of HEL, need to recognize all three TCR contact residues. In contrast, the type B T cells recognize the peptide given exogenously, but not when processed: these T cells recognize either one of the peripheral TCR contact residues, indicating a much more flexible interaction of peptide with I-A(k) molecules. We discuss the mode of generation of the various T cells and their biological relevance.

PMID:
12084929
[PubMed - indexed for MEDLINE]
PMCID:
PMC124386
Free PMC Article

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