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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 ?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.

SUBMITTER: Yin L 

PROVIDER: S-EPMC3494899 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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

Yin Lei L   Crawford Frances F   Marrack Philippa P   Kappler John W JW   Dai Shaodong S  

Proceedings of the National Academy of Sciences of the United States of America 20121022 45


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 ge  ...[more]

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