首页> 外文OA文献 >Characterization of thymus-derived lymphocytes expressing Ti alpha-beta CD3 gamma delta epsilon zeta-zeta, Ti alpha-beta CD3 gamma delta epsilon eta-eta or Ti alpha-beta CD3 gamma delta epsilon zeta-zeta/zeta- eta antigen receptor isoforms: analysis by gene transfection
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Characterization of thymus-derived lymphocytes expressing Ti alpha-beta CD3 gamma delta epsilon zeta-zeta, Ti alpha-beta CD3 gamma delta epsilon eta-eta or Ti alpha-beta CD3 gamma delta epsilon zeta-zeta/zeta- eta antigen receptor isoforms: analysis by gene transfection

机译:表达Tiα-βCD3γδε-ζ,Tiα-βCD3γδeta-eta或Tiα-βCD3γεζ/ζ-ζ抗原受体亚型的胸腺衍生淋巴细胞的特征:基因转染分析

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摘要

To characterize the function of the CD3 eta subunit of the T cell receptor (TCR), we have used cDNAs encoding CD3 zeta, CD3 eta, or both to reconstitute a variant of a cytochrome c-specific, I-Ek-restricted murine T cell hybridoma, termed MA5.8, which lacks CD3 zeta and CD3 eta proteins. We provide direct evidence that assembly and surface expression of TCRs can be mediated by either of these subunits separately or together. However, the level of TCR expression on zeta transfectants is up to one order of magnitude greater than that on eta transfectants, implying that CD3 eta is weakly associated with the pentameric Ti alpha-beta CD3 gamma delta epsilon complex and/or inefficient at salvaging the incomplete TCR from lysosomal degradation. As a component of the TCR, the CD3 eta subunit preferentially forms a heterodimer with CD3 zeta, but is also able to form a CD3 eta-eta homodimer. Crosslinking of Ti alpha-beta CD3 gamma delta epsilon zeta- zeta, Ti alpha-beta CD3 gamma delta epsilon eta-eta, or Ti alpha-beta CD3 gamma delta epsilon zeta-zeta/zeta-eta TCR isotypes with anti-CD3 epsilon monoclonal antibody or a cytochrome c peptide epitope on I-Ek antigen-presenting cells mediates signal transduction resulting in reversible cell-cycle arrest of transfected clones. Given the potential for diversity of signals generated by these functional TCR isotypes and the expression of the CD3 eta gene product in the thymus, CD3 eta is likely to play a role in selection and/or activation of thymocytes during development.
机译:为了表征T细胞受体(TCR)CD3 eta亚基的功能,我们使用了编码CD3 zeta,CD3 eta或两者的cDNA重构了细胞色素c特异性,I-Ek限制性的鼠类T细胞的变体杂交瘤,称为MA5.8,缺少CD3 zeta和CD3 eta蛋白。我们提供直接的证据表明,TCRs的组装和表面表达可以由这些亚基单独或共同介导。然而,Zeta转染子上的TCR表达水平比eta转染子上的TCR表达水平高一个数量级,这表明CD3 eta与五聚体Tiα-βCD3γ-δε复合物弱相关和/或挽救CD3 eta效率低下。溶酶体降解导致TCR不完全。作为TCR的成分,CD3 eta亚基优先与CD3 zeta形成异二聚体,但也能够形成CD3 eta-eta同型二聚体。 Tiα-βCD3γδzeta-eta,Tiα-βCD3γδzeta-eta或Tiα-βCD3 gammaδzeta-zeta / zeta-eta TCR同种型与抗CD3ε单克隆抗体的交联I-Ek抗原呈递细胞上的抗体或细胞色素C肽表位介导信号转导,导致转染克隆的细胞周期阻滞可逆。考虑到由这些功能性TCR同种型产生的信号具有多样性的潜力,以及胸腺中CD3 eta基因产物的表达,CD3 eta在发育过程中可能在胸腺细胞的选择和/或激活中发挥作用。

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