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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Diabetogenic T cells recognize insulin bound to IA~(g7) in an unexpected, weakly binding register
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Diabetogenic T cells recognize insulin bound to IA~(g7) in an unexpected, weakly binding register

机译:致糖尿病的T细胞在意外的弱结合寄存器中识别与IA〜(g7)结合的胰岛素

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摘要

A peptide derived from the insulin B chain contains a major epitope for diabetogenic CD4~+ T cells in the NOD mouse model of type 1 diabetes (T1D). This peptide can fill the binding groove of the NOD MHCII molecule, IA~(97), in a number of ways or "registers." We show here that a diverse set of NOD anti-insulin T cells all recognize this peptide bound in the same register. Surprisingly, this register results in the poorest binding of peptide to IA~(g7). The poor binding is due to an incompatibility between the p9 amino acid of the peptide and the unique IA~(g7) p9 pocket polymorphisms that are strongly associated with susceptibility to T1D. Our findings suggest that the association of autoimmunity with particular MHCII alleles may be do to poorer, rather than more favorable, binding of the critical self-epitopes, allowing T-cell escape from thymic deletion.
机译:在1型糖尿病(T1D)的NOD小鼠模型中,衍生自胰岛素B链的肽包含一个致糖尿病CD4 + T细胞的主要表位。该肽可以以多种方式或“配准”填充NOD MHCII分子IA_(97)的结合槽。我们在这里表明,各种各样的NOD抗胰岛素T细胞都识别结合在同一寄存器中的该肽。出人意料的是,该寄存器导致肽与IA_(g7)的结合最差。不良的结合是由于该肽的p9氨基酸与独特的IA〜(g7)p9口袋多态性之间的不相容性,该多态性与对T1D的敏感性密切相关。我们的发现表明,自身免疫与特定的MHCII等位基因的关联可能与关键的自身表位的结合较弱而不是更有利有关,从而使T细胞从胸腺缺失中逃脱。

著录项

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  • 作者单位

    lntegrated Department of Immunology, University of Colorado and National Jewish Health, Denver, CO 80206 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206;

    rnBarbara Davis Center for Childhood Diabetes, Aurora, CO 80045;

    rnlntegrated Department of Immunology, University of Colorado and National Jewish Health, Denver, CO 80206 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206;

    rnlntegrated Department of Immunology, University of Colorado and National Jewish Health, Denver, CO 80206 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206;

    rnlntegrated Department of Immunology, University of Colorado and National Jewish Health, Denver, CO 80206 Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045;

    rnlntegrated Department of Immunology, University of Colorado and National Jewish Health, Denver, CO 80206 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    diabetes; autoimmunity; tolerance; self-antigens; antigen presentation;

    机译:糖尿病;自身免疫公差;自身抗原抗原呈递;

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