T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy

摘要

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 eNH_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 p-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.