Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, 97239, USA.
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.
Sci Rep. 2020 Nov 27;10(1):20778. doi: 10.1038/s41598-020-77563-4.
Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. MAIT cells recognize bacterial small molecule metabolites presented on the Class I-like molecule MR1. As with other Class I and Class II molecules, MR1 can likely sample ligands in the intracellular environment through multiple cellular pathways. Rab6, a small GTPase that regulates a number of endosomal trafficking pathways including retrograde transport to the trans-Golgi network (TGN), is involved in the presentation of ligands from Mycobacterium tuberculosis (Mtb) to MAIT cells. The Rab6-mediated trafficking pathway contains endosomal compartments that share features with the Mtb intracellular compartment. Using inducible expression of MR1, this study demonstrates that Rab6 regulates the recycling of MR1 molecules from the cell surface through endosomal trafficking compartments to the TGN. This Rab6-dependent pool of recycled MR1, which is available for reloading with ligands from bacterial pathogens like Mtb, may be important for early recognition of infected cells by MAIT cells in the lung.
黏膜相关不变 T（MAIT）细胞是一种先天样 T 细胞亚群，在对肺部细菌和病毒病原体的早期反应中很重要。MAIT 细胞识别在类 I 样分子 MR1 上呈现的细菌小分子代谢物。与其他 I 类和 II 类分子一样，MR1 可能通过多种细胞途径从细胞内环境中取样配体。Rab6 是一种小 GTPase，可调节包括逆行运输到反式高尔基体网络（TGN）在内的多种内体运输途径，参与结核分枝杆菌（Mtb）配体向 MAIT 细胞的呈递。Rab6 介导的运输途径包含与 Mtb 细胞内隔室具有共同特征的内体隔室。本研究通过诱导表达 MR1，证明 Rab6 通过内体运输隔室调节 MR1 分子从细胞表面的再循环到 TGN。这种 Rab6 依赖性的再循环 MR1 池可用于从细菌病原体（如 Mtb）加载配体，这可能对 MAIT 细胞在肺部早期识别受感染细胞很重要。
