Endogenous MHC-related protein 1 is transiently expressed on the plasma membrane in a conformation that activates mucosal-associated invariant T cells.
Endogenous MHC-related protein 1 is transiently expressed on the plasma membrane in a conformation that activates mucosal-associated invariant T cells.
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DOI：
10.4049/jimmunol.1003254
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Hansen TH
中科院分区：
文献类型：
--
作者：
Chua WJ;Kim S;Myers N;Huang S;Yu L;Fremont DH;Diamond MS;Hansen TH
粘膜相关不变T细胞（MAIT）的发育依赖于Ib类分子MHC相关蛋白1（MR 1）、肠道细菌和胸腺。此外，最近的研究表明，在细菌识别中，MR 1呈递给MAIT细胞，尽管其机制尚不明确。然而，令人惊讶的是，MR 1的表面表达一直难以检测血清学，尽管无处不在的检测MR 1转录本和细胞内蛋白。在这篇文章中，我们定义了一种独特的单克隆抗体，能够稳定内源性小鼠MR 1在细胞表面，导致增强小鼠MAIT细胞活化。我们的研究结果表明，在基础条件下，内源性MR 1瞬时访问细胞表面，从而调和上述血清学和功能研究。此外，使用这种方法，双阳性胸腺细胞，巨噬细胞和树突状细胞被鉴定为MAIT细胞发育和活化的潜在APC。基于MR 1表达的这种模式，推测MR 1的组成型表达可能不利于维持肠道中的免疫稳态和/或检测粘膜组织中的病原菌是有趣的。
The development of mucosal-associated invariant T (MAIT) cells is dependent upon the class Ib molecule MHC-related protein 1 (MR1), commensal bacteria, and a thymus. Furthermore, recent studies have implicated MR1 presentation to MAIT cells in bacteria recognition, although the mechanism remains undefined. Surprisingly, however, surface expression of MR1 has been difficult to detect serologically, despite ubiquitous detection of MR1 transcripts and intracellular protein. In this article, we define a unique mAb capable of stabilizing endogenous mouse MR1 at the cell surface, resulting in enhanced mouse MAIT cell activation. Our results demonstrated that under basal conditions, endogenous MR1 transiently visits the cell surface, thus reconciling the aforementioned serologic and functional studies. Furthermore, using this approach, double-positive thymocytes, macrophages, and dendritic cells were identified as potential APCs for MAIT cell development and activation. Based on this pattern of MR1 expression, it is intriguing to speculate that constitutive expression of MR1 may be detrimental for maintenance of immune homeostasis in the gut and/or detection of pathogenic bacteria in mucosal tissues.
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