Früh K, Gruhler A, Krishna R M, Schoenhals G J
R.W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Immunol Rev. 1999 Apr;168:157-66. doi: 10.1111/j.1600-065x.1999.tb01290.x.
Peptide fragments from proteins of intracellular pathogens such as viruses are displayed at the cell surface by MHC class I molecules thus enabling surveillance by cytotoxic T cells. Peptides are produced in the cytosol by proteasomal degradation and translocated into the endoplasmic reticulum by the peptide transporter TAP. Empty MHC class I molecules associate with TAP prior to their acquisition of peptides, a process which is assisted and controlled by a series of chaperones. The first part of this review summarizes our current knowledge of this assembly pathway and describes recent observations that tapasin functions as an endoplasmic reticulum retention molecule for empty MHC class I molecules. To defeat the presentation of virus-derived peptides, several DNA viruses have devised strategies to interfere with MHC class I assembly. Although these evasion strategies have evolved independently and differ mechanistically they often target the same step in this pathway. We compare escape mechanisms of different viruses with particular emphasis on the retention of newly synthesized MHC class I molecules in the endoplasmic reticulum and the inhibition of peptide transport by viral proteins.
细胞内病原体（如病毒）蛋白质的肽片段由MHC I类分子呈递于细胞表面，从而使得细胞毒性T细胞能够进行监测。肽在胞质溶胶中通过蛋白酶体降解产生，并由肽转运体TAP转运至内质网。空载的MHC I类分子在获取肽之前与TAP结合，这一过程由一系列伴侣蛋白协助和控制。本综述的第一部分总结了我们目前对这一装配途径的认识，并描述了近期的观察结果，即塔帕辛作为空载MHC I类分子的内质网滞留分子发挥作用。为了阻止病毒衍生肽的呈递，几种DNA病毒已设计出干扰MHC I类装配的策略。尽管这些逃避策略是独立进化的，且机制不同，但它们通常靶向该途径中的同一步骤。我们比较不同病毒的逃逸机制，特别强调新合成的MHC I类分子在内质网中的滞留以及病毒蛋白对肽转运的抑制。
