CD3ε富含脯氨酸的序列控制预选CD4+CD8+胸腺细胞上T细胞抗原受体的表达及其信号传导能力。

The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes.

作者信息

Mingueneau Michaël, Sansoni Amandine, Grégoire Claude, Roncagalli Romain, Aguado Enrique, Weiss Arthur, Malissen Marie, Malissen Bernard

机构信息

Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique UMR6102, 13288 Marseille Cedex 9, France.

出版信息

Nat Immunol. 2008 May;9(5):522-32. doi: 10.1038/ni.1608. Epub 2008 Apr 13.

DOI:10.1038/ni.1608

PMID:18408722

Abstract

Antigen recognition by T cell antigen receptors (TCRs) is thought to 'unmask' a proline-rich sequence (PRS) present in the CD3epsilon cytosolic segment, which allows it to trigger T cell activation. Using 'knock-in' mice with deletion of the PRS, we demonstrate here that elimination of the CD3epsilon PRS had no effect on mature T cell responsiveness. In contrast, in preselection CD4+CD8+ thymocytes, the CD3epsilon PRS acted together with the adaptor protein SLAP to promote CD3zeta degradation, thereby contributing to downregulation of TCR expression on the cell surface. In addition, analysis of CD4+CD8+ thymocytes of TCR-transgenic mice showed that the CD3epsilon PRS enhanced TCR sensitivity to weak ligands. Our results identify previously unknown functions for the evolutionarily conserved CD3epsilon PRS at the CD4+CD8+ developmental stage and suggest a rather limited function in mature T cells.

摘要

T细胞抗原受体（TCR）对抗原的识别被认为会“暴露”CD3ε胞质段中存在的富含脯氨酸的序列（PRS），这使其能够触发T细胞活化。我们利用缺失PRS的“敲入”小鼠证明，消除CD3ε PRS对成熟T细胞反应性没有影响。相反，在预选的CD4⁺CD8⁺胸腺细胞中，CD3ε PRS与衔接蛋白SLAP共同作用，促进CD3ζ降解，从而有助于下调细胞表面TCR的表达。此外，对TCR转基因小鼠的CD4⁺CD8⁺胸腺细胞的分析表明，CD3ε PRS增强了TCR对弱配体的敏感性。我们的结果确定了进化保守的CD3ε PRS在CD4⁺CD8⁺发育阶段以前未知的功能，并表明其在成熟T细胞中的功能相当有限。