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1: Nat Immunol. 2007 Apr;8(4):388-97. Epub 2007 Feb 25.
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Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes.

Felix NJ, Donermeyer DL, Horvath S, Walters JJ, Gross ML, Suri A, Allen PM.

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

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]