Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Semin Cell Dev Biol. 2010 Jul;21(5):512-9. doi: 10.1016/j.semcdb.2009.12.013. Epub 2010 Jan 5.
Class I molecules of the major histocompatibility complex play a vital role in cellular immunity, reporting on the presence of viral or tumor-associated antigens by binding peptide fragments of these proteins and presenting them to cytotoxic T cells at the cell surface. The folding and assembly of class I molecules is assisted by molecular chaperones and folding catalysts that comprise the general ER quality control system which also monitors the integrity of the process, disposing of misfolded class I molecules through ER associated degradation (ERAD). Interwoven with general ER quality control are class I-specific components such as the peptide transporter TAP and the tapasin-ERp57 chaperone complex that supply peptides and monitor their loading onto class I molecules. This ensures that at the cell surface class I molecules will possess mainly optimal peptides with a long half-life. In this review we discuss these processes as well as a number of strategies that viruses have evolved to subvert normal class I assembly within the ER and thereby evade immune recognition by cytotoxic T cells.
主要组织相容性复合体 I 类分子在细胞免疫中发挥着至关重要的作用，通过结合这些蛋白质的肽段，并将其呈递到细胞表面的细胞毒性 T 细胞上，从而报告病毒或肿瘤相关抗原的存在。I 类分子的折叠和组装由分子伴侣和折叠催化剂辅助，这些分子伴侣和折叠催化剂构成了一般的内质网质量控制系统，该系统还监测着这一过程的完整性，通过内质网相关降解（ERAD）来处理错误折叠的 I 类分子。与一般的内质网质量控制交织在一起的是 I 类分子特异性成分，如肽转运蛋白 TAP 和 tapasin-ERp57 伴侣复合物，它们提供肽并监测其加载到 I 类分子上。这确保了在细胞表面，I 类分子将主要拥有具有长半衰期的最佳肽段。在这篇综述中，我们讨论了这些过程，以及病毒进化出的许多策略，这些策略旨在破坏内质网中正常的 I 类分子组装，从而逃避细胞毒性 T 细胞的免疫识别。
