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One of the CD3ε Subunits within a T Cell Receptor Complex Lies in Close Proximity to the Cβ FG Loop

机译:T细胞受体复合物中的CD3ε亚基之一与CβFG环非常接近

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摘要

A recent crystal structure of the N15 α/β-T cell receptor (TCR) in complex with an Fab derived from the H57 Cβ-specific monoclonal antibody (mAb) shows the mAb fragment interacting with the elongated FG loop of the Cβ domain. This loop creates one side wall of a cavity within the TCR Ti-α/β constant region module (CαCβ) while the CD and EF loops of the Cα domain form another wall. The cavity size is sufficient to accommodate a single nonglycosylated Ig domain such as the CD3ε ectodomain. By using specific mAbs to mouse TCR-β (H57) and CD3ε (2C11) subunits, we herein provide evidence that only one of the two CD3ε chains within the TCR complex is located in close proximity to the TCR Cβ FG loop, in support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3ε genes shows that the heterologous human CD3ε component can replace the mouse CD3ε at this site. The location of one CD3ε subunit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development.
机译:N15α/β-T细胞受体(TCR)与源自H57Cβ特异性单克隆抗体(mAb)的Fab形成复合体的最新晶体结构显示,mAb片段与Cβ域的拉长FG环相互作用。该回路在TCRTi-α/β恒定区模块(CαCβ)内形成空腔的一个侧壁,而Cα域的CD和EF回路形成另一壁。腔的大小足以容纳单个非糖基化的Ig域,例如CD3ε胞外域。通过使用针对小鼠TCR-β(H57)和CD3ε(2C11)亚基的特异性mAb,我们在本文中提供了证据,证明TCR复合物中两条CD3ε链中只有一条紧邻TCRCβFG环,以支持以上概念。此外,对从表达人和小鼠CD3ε基因的转基因小鼠分离的T细胞的分析表明,异源人CD3ε组分可以在此位点取代小鼠CD3ε。刚性恒定域模块内一个CD3ε亚基的位置对整个T细胞发育过程中的信号转导机制有影响。

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