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标题：T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy
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作者：Lei Yin ; Frances Crawford ; Philippa Marrack 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：45
页码：18517-18522
DOI：10.1073/pnas.1215928109
语种：English
出版社：The National Academy of Sciences of the United States of America
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 {varepsilon}NH2 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{beta} 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 {beta}-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.
关键词：antigen presentation ; hypersensitivity ; peptide display library ; crystal structure ; metal recognition