Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
F1000Res. 2020 Sep 28;9. doi: 10.12688/f1000research.26935.1. eCollection 2020.
Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I-peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.
主要组织相容性复合体 I 类（MHC-I）蛋白通过向 CD8+T 细胞的抗原受体呈递抗原或突变肽以及与自然杀伤（NK）细胞的受体结合来介导针对病原体和癌症的免疫监视。在人类中，MHC-I 分子高度多态性。MHC-I 的变异允许在细胞表面显示数千种独特的肽。最近的质谱研究揭示了个体 MHC-I 变体的肽组的独特和共同特征。MHC-I-肽复合物的细胞表面表达需要许多细胞内组装因子的功能，包括抗原呈递相关转运体（TAP）、tapasin、钙网蛋白、ERp57、TAP 结合蛋白相关（TAPBPR）、内质网氨肽酶（ERAPs）和蛋白酶体。最近的研究提供了对这些因子的结构特征的重要见解，这些因子控制 MHC-I 的组装以及肽交换的机制。MHC-I 分子的构象感应介导细胞内 MHC-I 组装的质量控制，并有助于 CD8 在细胞表面的免疫识别。最近的研究还表明，几种 MHC-I 变体可以遵循非常规的组装途径到细胞表面，赋予选择性免疫优势，可用于免疫治疗。
