Hengel H, Esslinger C, Pool J, Goulmy E, Koszinowski U H
Department of Virology, University of Heidelberg, Germany.
J Gen Virol. 1995 Dec;76 ( Pt 12):2987-97. doi: 10.1099/0022-1317-76-12-2987.
CD8+ cytotoxic T cell (CTL) clones with specificity for defined minor and major histocompatibility (H) antigens were used to monitor antigen presentation in human cytomegalovirus (HCMV)-infected skin fibroblasts. At the immediate early stage of virus replication antigen presentation was intact, but was abolished during the early and late phase. Lack of CTL recognition was not selective for certain antigens but was associated with decreased steady state levels of nascent MHC class I complexes and unassembled MHC class I heavy chains, whereas free beta 2-microglobulin remained abundant. HCMV also affected the stability of both immature endoglycosidase H (Endo H)-sensitive and mature Endo H-resistant MHC class I molecules, suggesting that the virus interferes with antigen presentation at more than one step during maturation of the MHC class I complex. The action of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) lifted the block of MHC class I complex formation by stimulating synthesis, assembly and stability of MHC class I molecules. This resulted in restored antigen presentation provided that cells were exposed to the factors before HCMV infection. Because few MHC molecules suffice for CTL recognition these cytokines compensated for the negative viral effect on the antigen presentation function. Nevertheless, the viral interference with MHC class I complex formation was still active. The data imply that specific cytokines limit the immune evasion potential of HCMV from CD8+ T lymphocyte control.
用对特定的次要和主要组织相容性（H）抗原具有特异性的CD8 + 细胞毒性T细胞（CTL）克隆来监测人巨细胞病毒（HCMV）感染的皮肤成纤维细胞中的抗原呈递。在病毒复制的即刻早期阶段，抗原呈递是完整的，但在早期和晚期阶段被消除。CTL识别的缺乏并非对某些抗原具有选择性，而是与新生MHC I类复合物和未组装的MHC I类重链的稳态水平降低有关，而游离的β2-微球蛋白仍然丰富。HCMV还影响未成熟的内切糖苷酶H（Endo H）敏感和成熟的Endo H抗性MHC I类分子的稳定性，这表明该病毒在MHC I类复合物成熟过程中的多个步骤干扰抗原呈递。干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）的作用通过刺激MHC I类分子的合成、组装和稳定性解除了MHC I类复合物形成的阻滞。如果细胞在HCMV感染之前暴露于这些因子，这会导致抗原呈递恢复。因为很少的MHC分子就足以进行CTL识别，所以这些细胞因子补偿了病毒对抗原呈递功能的负面作用。然而，病毒对MHC I类复合物形成的干扰仍然存在。数据表明特定的细胞因子限制了HCMV逃避CD8 + T淋巴细胞控制的免疫逃逸潜力。
