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 εNH₂ 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.