Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
Semin Immunol. 2015 Mar;27(2):125-37. doi: 10.1016/j.smim.2015.03.010. Epub 2015 Apr 15.
The MHC class I antigen presentation pathway enables cells infected with intracellular pathogens to signal the presence of the invader to the immune system. Cytotoxic T lymphocytes are able to eliminate the infected cells through recognition of pathogen-derived peptides presented by MHC class I molecules at the cell surface. In the course of evolution, many viruses have acquired inhibitors that target essential stages of the MHC class I antigen presentation pathway. Studies on these immune evasion proteins reveal fascinating strategies used by viruses to elude the immune system. Viral immunoevasins also constitute great research tools that facilitate functional studies on the MHC class I antigen presentation pathway, allowing the investigation of less well understood routes, such as TAP-independent antigen presentation and cross-presentation of exogenous proteins. Viral immunoevasins have also helped to unravel more general cellular processes. For instance, basic principles of ER-associated protein degradation via the ubiquitin-proteasome pathway have been resolved using virus-induced degradation of MHC class I as a model. This review highlights how viral immunoevasins have increased our understanding of MHC class I-restricted antigen presentation.
MHC I 类抗原呈递途径使被细胞内病原体感染的细胞能够将入侵物的存在信号传递给免疫系统。细胞毒性 T 淋巴细胞能够通过识别 MHC I 类分子在细胞表面呈现的病原体衍生肽来消除受感染的细胞。在进化过程中,许多病毒已经获得了针对 MHC I 类抗原呈递途径关键阶段的抑制剂。对这些免疫逃逸蛋白的研究揭示了病毒逃避免疫系统的迷人策略。病毒免疫逃逸蛋白也是强大的研究工具,它们促进了对 MHC I 类抗原呈递途径的功能研究,允许研究不太为人理解的途径,如 TAP 非依赖性抗原呈递和外源性蛋白的交叉呈递。病毒免疫逃逸蛋白也有助于阐明更普遍的细胞过程。例如,通过使用 MHC I 类的病毒诱导降解作为模型,已经解决了通过泛素-蛋白酶体途径进行 ER 相关蛋白降解的基本原理。这篇综述强调了病毒免疫逃逸蛋白如何提高我们对 MHC I 类限制的抗原呈递的理解。