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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position.
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Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position.

机译：CD8 alpha beta / MHC I类相互作用的结构基础：聚焦识别可将CD8 beta定位于T细胞近端位置。

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摘要

In the immune system, B cells, dendritic cells, NK cells, and T lymphocytes all respond to signals received via ligand binding to receptors and coreceptors. Although the specificity of T cell recognition is determined by the interaction of T cell receptors with MHC/peptide complexes, the development of T cells in the thymus and their sensitivity to Ag are also dependent on coreceptor molecules CD8 (for MHC class I (MHCI)) and CD4 (for MHCII). The CD8alphabeta heterodimer is a potent coreceptor for T cell activation, but efforts to understand its function fully have been hampered by ignorance of the structural details of its interactions with MHCI. In this study we describe the structure of CD8alphabeta in complex with the murine MHCI molecule H-2D(d) at 2.6 A resolution. The focus of the CD8alphabeta interaction is the acidic loop (residues 222-228) of the alpha3 domain of H-2D(d). The beta subunit occupies a T cell membrane proximal position, defining the relative positions of the CD8alpha and CD8beta subunits. Unlike the CD8alphaalpha homodimer, CD8alphabeta does not contact the MHCI alpha(2)- or beta(2)-microglobulin domains. Movements of the CD8alpha CDR2 and CD8beta CDR1 and CDR2 loops as well as the flexibility of the H-2D(d) CD loop facilitate the monovalent interaction. The structure resolves inconclusive data on the topology of the CD8alphabeta/MHCI interaction, indicates that CD8beta is crucial in orienting the CD8alphabeta heterodimer, provides a framework for understanding the mechanistic role of CD8alphabeta in lymphoid cell signaling, and offers a tangible context for design of structurally altered coreceptors for tumor and viral immunotherapy.
机译：在免疫系统中，B细胞，树突状细胞，NK细胞和T淋巴细胞都对通过配体与受体和共受体结合而接收到的信号作出反应。尽管T细胞识别的特异性取决于T细胞受体与MHC /肽复合物的相互作用，但胸腺中T细胞的发育及其对Ag的敏感性也取决于共受体分子CD8（对于MHC I类（MHCI） ）和CD4（用于MHCII）。 CD8alphabeta异二聚体是有效的T细胞活化共受体，但由于对其与MHCI相互作用的结构细节的了解不清，阻碍了充分理解其功能的努力。在这项研究中，我们描述了CD8alphabeta与小鼠MHCI分子H-2D（d）在2.6 A分辨率下的复合结构。 CD8alphabeta相互作用的重点是H-2D（d）的alpha3域的酸性环（残基222-228）。 β亚基占据着T细胞膜的近端位置，定义了CD8alpha和CD8beta亚基的相对位置。与CD8alphaalpha同型二聚体不同，CD8alphabeta不接触MHCI alpha（2）-或beta（2）-微球蛋白结构域。 CD8alpha CDR2和CD8beta CDR1和CDR2环的运动以及H-2D（d）CD环的灵活性促进了单价相互作用。该结构解析了关于CD8alphabeta / MHCI相互作用的拓扑结构的不确定性数据，表明CD8beta在定向CD8alphabeta异二聚体中至关重要，为理解CD8alphabeta在淋巴样细胞信号传导中的机械作用提供了框架，并为结构设计提供了切实的环境改变了用于肿瘤和病毒免疫治疗的共受体。

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