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Dynamics of MHC-I molecules in the antigen processing and presentation pathway.
Current opinion in immunology Pub Date : 2021-06-18 , DOI: 10.1016/j.coi.2021.04.012
Hau V Truong 1 , Nikolaos G Sgourakis 1
Affiliation  

The endogenous antigen processing and presentation (APP) is a fundamental pathway found in jawed vertebrates, which allows for a set of epitope peptides sampled from the intracellular proteome to be assembled and displayed on class I proteins of the major histocompatibility complex (MHC-I). Peptide/MHC-I antigens enable different aspects of adaptive immunity to emerge, by providing a basis for recognition of self vs. non-self by T cells and Natural Killer (NK) cells. Pioneering studies of pMHC-I molecules and their higher-order protein complexes with molecular chaperones and membrane receptors have gleaned important insights into the peptide loading and antigen recognition mechanisms. While X-ray and cryoEM structures have provided us with static snapshots of different MHC-I assembly stages, complementary biophysical techniques have revealed that MHC-I molecules are highly mobile on a range of biologically relevant timescales, which bears importance for their assembly, peptide repertoire selection, membrane display and turnover. This review summarizes insights gained from experimental and simulation studies aimed at investigating MHC-I dynamics, and their functional implications.

中文翻译:

MHC-I 分子在抗原加工和呈递途径中的动态。

内源抗原加工和呈递 (APP) 是有颌脊椎动物中发现的基本途径,它允许从细胞内蛋白质组中采样的一组表位肽组装并展示在主要组织相容性复合体 (MHC-I) 的 I 类蛋白质上。肽/MHC-I 抗原为 T 细胞和自然杀伤 (NK) 细胞提供识别自身与非自身的基础,从而使适应性免疫的不同方面得以出现。对 pMHC-I 分子及其与分子伴侣和膜受体的高阶蛋白质复合物的开创性研究已经收集了有关肽负载和抗原识别机制的重要见解。虽然 X 射线和冷冻电镜结构为我们提供了不同 MHC-I 组装阶段的静态快照,但互补的生物物理技术表明,MHC-I 分子在一系列生物学相关的时间尺度上具有高度的移动性,这对于它们的组装、肽、剧目选择、影片展示和周转。这篇综述总结了从旨在研究 MHC-I 动力学及其功能含义的实验和模拟研究中获得的见解。
更新日期:2021-06-18
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