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

Nathan J. Felix, David L. Donermeyer, Stephen Horvath, James J. Walters, Michael L. Gross, Anish Suri, Paul M. Allen

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


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-Ek-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-Ek 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.

Original languageEnglish
Pages (from-to)388-397
Number of pages10
JournalNature immunology
Issue number4
StatePublished - Apr 2007


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