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Evidence for a functional sidedness to the αβTCR

机译:αβTCR功能方面的证据

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摘要

The T cell receptor (TCR) and associated CD3γε, δε, and ζζ signaling dimers allow T cells to discriminate between different antigens and respond accordingly, but our knowledge of how these parts fit and work together is incomplete. In this study, we provide additional evidence that the CD3 heterodimers congregate on one side of the TCR in both the αβ and γδTCR-CD3 complexes. We also report that the other side of the αβTCR mediates homo-typic αβTCR interactions and signaling. Specifically, an erythro-poietin receptor-based dimerization assay was used to show that, upon complex assembly, the CD3ε chains of two CD3 heterodimers are arranged side-by-side in both the αβ and γδTCR-CD3 complexes. This system was also used to show that αβTCRs can dimerize in the cell membrane and that mutating the unusual outer strands of the Cα domain impairs this dimerization. Finally, we present data showing that, for CD4 T cells, the mutations that impair αβTCR dimerization also alter ligand-induced calcium mobilization, TCR accumulation at the site of pMHC contact, and polarization toward the site of antigen contact. These data reveal a "functional-sidedness" to the βTCR constant region, with dimerization occurring on the side of the TCR opposite from where the CD3 heterodimers are located.
机译:T细胞受体(TCR)和相关的CD3γε,δε和ζζ信号二聚体使T细胞能够区分不同的抗原并做出相应的反应,但是我们对这些部分如何装配和协同工作的了解尚不完善。在这项研究中,我们提供了其他证据,证明CD3异二聚体聚集在TCR的αβ和γδTCR-CD3复合物中。我们还报告说,αβTCR的另一端介导同型αβTCR相互作用和信号传导。具体而言,使用基于促红细胞生成素受体的二聚化分析显示,在复合体组装后,两个CD3异二聚体的CD3ε链在αβ和γδTCR-CD3复合体中并排排列。该系统还用于显示αβTCR可以在细胞膜中二聚化,并且突变Cα域的异常外链会削弱这种二聚化。最后,我们提供的数据表明,对于CD4 T细胞,损害αβTCR二聚化的突变还改变了配体诱导的钙动员,pMHC接触位点的TCR积累和朝向抗原接触位点的极化。这些数据揭示了βTCR恒定区的“功能性”,二聚化发生在TCR的与CD3异二聚体所在的相反的一侧。

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  • 作者单位

    Department of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305 Graduate Program in Immunology, Chevy Chase, MD 20815;

    rnStanford University School of Medicine, Stanford, CA 94305 Graduate Program in Biophysics, Chevy Chase, MD 20815;

    rnStanford University School of Medicine, Stanford, CA 94305 CCIS/ITI Summer High School Research Program, Chevy Chase, MD 20815;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305 Nomis Center for Immunobiology and Microbial Pathogenesis, Waitt Advanced Biophotonics Center, the Salk Institute, La Jolla, CA 92037;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305 Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305;

    rnStanford University School of Medicine, Stanford, CA 94305 Department of Molecular and Cellular Physiology, Chevy Chase, MD 20815 Department of Structural Biology, Chevy Chase, MD 20815 The Howard Hughes Medical Institute, Chevy Chase, MD 20815;

    rnDepartment of Microbiology and Immunology, Chevy Chase, MD 20815 Stanford University School of Medicine, Stanford, CA 94305 The Howard Hughes Medical Institute, Chevy Chase, MD 20815;

  • 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

    T cell; T cell receptor; CD3; organization; dimerization; signaling;

    机译:T细胞T细胞受体;CD3;组织;二聚化发信号;

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