4h26

Publication Abstract from PubMed

T cell-mediated allergy to Ni(++) is one of the most common forms of allergic contact dermatitis, but how the T-cell receptor (TCR) recognizes Ni(++) is unknown. We studied a TCR from an allergic patient that recognizes Ni(++) bound to the MHCII molecule DR52c containing an unknown self-peptide. We identified mimotope peptides that can replace both the self-peptide and Ni(++) in this ligand. They share a p7 lysine whose epsilonNH(2) group is surface-exposed when bound to DR52c. Whereas the TCR uses germ-line complementary-determining region (CDR)1/2 amino acids to dock in the conventional diagonal mode on the mimotope-DR52c complex, the interface is dominated by the TCR Vbeta CDR3 interaction with the p7 lysine. Mutations in the TCR CDR loops have similar effects on the T-cell response to either the mimotope or Ni(++) ligand. We suggest that the mimotope p7 lysine mimics Ni(++) in the natural TCR ligand and that MHCII beta-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.

T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy.,Yin L, Crawford F, Marrack P, Kappler JW, Dai S Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18517-22. doi:, 10.1073/pnas.1215928109. Epub 2012 Oct 22. PMID:23091041^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.