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Nat Immunol. 2007 Apr;8(4):388-97. Epub 2007 Feb 25.

Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes.

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  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63130, USA.

Abstract

The molecular basis underlying the specificity of alloreactive T cells for peptide-major histocompatibility complex ligands has been elusive. Here we describe a screen of 60 I-E(k)-alloreactive T cells and 83 naturally processed peptides that identified 9 reactive T cells. Three of the T cells responded to multiple, distinct peptides that shared no sequence homology. These T cells recognized each peptide-major histocompatibility complex ligand specifically and used a distinct constellation of I-E(k) contact residues for each interaction. Our studies show that alloreactive T cells have a 'germline-encoded' capacity to recognize multiple, distinct ligands and thus show 'polyspecificity', not degeneracy. Our findings help to explain the high frequency of alloreactive T cells and provide insight into the nature of T cell specificity.

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PMID:
17322886
[PubMed - indexed for MEDLINE]
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