Institute of Biochemistry, Biocenter, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany; email:
Annu Rev Biophys. 2020 May 6;49:135-161. doi: 10.1146/annurev-biophys-121219-081643. Epub 2020 Jan 31.
The fundamental process of adaptive immunity relies on the differentiation of self from nonself. Nucleated cells are continuously monitored by effector cells of the immune system, which police the peptide status presented via cell surface molecules. Recent integrative structural approaches have provided insights toward our understanding of how sophisticated cellular machineries shape such hierarchical immune surveillance. Biophysical and structural achievements were invaluable for defining the interconnection of many key factors during antigen processing and presentation, and helped to solve several conundrums that persisted for many years. In this review, we illuminate the numerous quality control machineries involved in different steps during the maturation of major histocompatibility complex class I (MHC I) proteins, from their synthesis in the endoplasmic reticulum to folding and trafficking via the secretory pathway, optimization of antigenic cargo, final release to the cell surface, and engagement with their cognate receptors on cytotoxic T lymphocytes.
适应性免疫的基本过程依赖于自我与非我之间的区分。有核细胞被免疫系统的效应细胞持续监测，这些效应细胞通过细胞表面分子来监测肽段状态。最近的综合结构方法为我们理解复杂的细胞机制如何塑造这种分层免疫监视提供了深入的认识。生物物理和结构方面的成就对于定义抗原加工和呈递过程中许多关键因素的相互关系非常有价值，并有助于解决多年来存在的一些难题。在这篇综述中，我们阐述了在主要组织相容性复合体 I 类 (MHC I) 蛋白成熟过程中涉及的众多质量控制机制，包括它们在内质网中的合成、通过分泌途径的折叠和运输、抗原货物的优化、最终释放到细胞表面以及与细胞毒性 T 淋巴细胞上的同源受体结合。
