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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Crystal structure of a γδ T-cell receptor specific for the human MHC class I homolog MICA
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Crystal structure of a γδ T-cell receptor specific for the human MHC class I homolog MICA

机译：人类MHC I类同系物MICA特异的γδT细胞受体的晶体结构

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摘要

γδ T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human γδ T cells of the V_δ1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumor-igenesis or viral infection. The crystal structure of an MIC-reacttve V_δ1 γδ T-cell receptor (TCR) showed expected overall structural homology to antibodies, αβ, and other γδ TCRs, but complementary determining region conformations and conservation of V_δ 1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunorecep-tor natural killer group 2, D (NKG2D), also expressed on γδ T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of γδ T-cell/target cell interfaces.
机译：γδT细胞在弥合先天免疫和适应性免疫方面起着重要作用，但其识别机制仍知之甚少。 V_δ1子集的人γδT细胞在肠道上皮细胞中占主导地位，并对MICA和MICB（MHC I类链相关，A和B； MIC）自身抗原产生反应，介导对肿瘤发生或病毒感染的反应。 MIC反应的V_δ1γδT细胞受体（TCR）的晶体结构显示出与抗体，αβ和其他γδTCR的预期整体结构同源性，但互补的确定区域构象和V_δ1的使用守恒表明其特征平整的潜在结合表面。同样，MIC也是激活的免疫受体天然杀伤剂组2 D（NKG2D）的配体，也表达于γδT细胞上。尽管MIC识别驱动激活所需的TCR依赖性刺激信号和NKG2D依赖性共刺激信号，但相互作用分析表明，两种受体的MIC结合是互斥的。相对结合动力学的分析建议顺序识别，为γδT细胞/靶细胞界面的时间组织定义了约束。

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  • 作者

    Bin Xu; Juan C. Pizarro; Margaret A. Holmes; Christine McBeth; Veronika Groh; Thomas Spies; Roland K. Strong;

  • 作者单位

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Structural Genomics Consortium, University of Toronto, Toronto, ON,Canada M5G 1L7;

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115;

    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

  • 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

    biacore; crystallography;

    机译：双核;晶体学;

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