The comings and goings of MHC class I molecules herald a new dawn in cross-presentation.
The comings and goings of MHC class I molecules herald a new dawn in cross-presentation.
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DOI：
10.1111/imr.12428
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发表时间：
2016-07
影响因子：
8.7
通讯作者：
Blander JM
中科院分区：
文献类型：
--
作者：
Blander JM
MHC I类(MHC-I)分子是交叉呈现的中心。它们被装载着来自外源来源的多肽，并显示在质膜上与CD8 T细胞通信，传递耐受或攻击的信息。交叉呈递的研究一直集中在抗原处理的空泡和胞浆途径的相对贡献以及MHC-I分子被加载的位置。虽然液泡加工产生的多肽被装载到液泡MHC-I分子上，但由蛋白酶体产生并由TAP运输的外源肽如何以及在哪里与MHC-I分子相遇以供装载一直是一个有争议的问题。树突状细胞中MHC-I分子的来源和运输在很大程度上被忽略了，因为人们认为这些分子来自内质网(ER)或质膜。新的研究显示，MHC-I分子集中在细胞内循环隔室(ERC)。这些池被迅速动员到携带微生物抗原的吞噬小体上，并在Toll样受体的控制下以信号依赖的方式进行。吞噬小体成为一个动态的中枢，接受来自多个来源的流量，内质网高尔基体中间隔间用于运送多肽装载机制，ERC用于部署MHC-I分子，警告CD8 T细胞感染。
MHC class I (MHC-I) molecules are the centerpieces of cross-presentation. They are loaded with peptides derived from exogenous sources and displayed on the plasma membrane to communicate with CD8 T cells, relaying a message of tolerance or attack. The study of cross-presentation has been focused on the relative contributions of the vacuolar versus cytosolic pathways of antigen processing and the location where MHC-I molecules are loaded. While vacuolar processing generates peptides loaded onto vacuolar MHC-I molecules, how and where exogenous peptides generated by the proteasome and transported by TAP meet MHC-I molecules for loading has been a matter of debate. The source and trafficking of MHC-I molecules in dendritic cells have largely been ignored under the expectation that these molecules came from the Endoplasmic reticulum (ER) or the plasma membrane. New studies reveal a concentrated pool of MHC-I molecules in the endocytic recycling compartment (ERC). These pools are rapidly mobilized to phagosomes carrying microbial antigens, and in a signal-dependent manner under the control of Toll-like receptors. The phagosome becomes a dynamic hub receiving traffic from multiple sources, the ER-Golgi intermediate compartment for delivering the peptide-loading machinery and the ERC for deploying MHC-I molecules that alert CD8 T cells of infection.