title: T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy.
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 εNH(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 Vβ 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 β-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.
authors.affiliation: Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Shaodong
authors.initials: S
authors.lastname: Dai
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D059810:HLA-DR Serological Subtypes / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009532:Nickel / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D059810:HLA-DR Serological Subtypes; C051104:HLA-DR52 antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D009532:Nickel; D008239:Lysine