Epitopes described in "T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy."

Article Authors:Lei Yin; Frances Crawford; Philippa Marrack; John W Kappler; Shaodong Dai
Article Title:T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy.
Reference Detail
Reference ID:1025226
Abstract: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 NH(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 V 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 -chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.
Affiliations:Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206, USA.
Reference Type:Literature
PubMed ID:23091041
Journal:Proc Natl Acad Sci U S A
Journal Volume:109
Article Pages:18517-22
Journal ISSN:0027-8424
Article Chemical List:Epitopes;HLA-DR Serological Subtypes;HLA-DR52 antigen;Peptides;Receptors, Antigen, T-Cell;Nickel;Lysine
Article MeSH List:Amino Acid Motifs; Amino Acid Sequence; Binding Sites(immunology); Dermatitis, Allergic Contact(immunology); Epitopes(chemistry; immunology); HLA-DR Serological Subtypes(immunology); Humans; Kinetics; Lysine(metabolism); Models, Molecular; Molecular Sequence Data; Nickel(immunology); Peptides(chemistry; immunology); Protein Structure, Secondary; Receptors, Antigen, T-Cell(immunology); T-Lymphocytes(immunology)
Curation Last Updated:2016-05-11 20:11:33