Cebulla Colleen M, Miller Daniel M, Zhang Yingxue, Rahill Brian M, Zimmerman Peter, Robinson John M, Sedmak Daniel D
Department of Pathology, Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA.
J Immunol. 2002 Jul 1;169(1):167-76. doi: 10.4049/jimmunol.169.1.167.
CD8(+) and CD4(+) T lymphocytes are important in controlling human CMV (HCMV) infection, but the virus has evolved protean mechanisms to inhibit MHC-based Ag presentation and escape T lymphocyte immunosurveillance. Herein, the interaction of HCMV with the MHC class II Ag presentation pathway was investigated in cells stably transfected with class II transactivator. Flow cytometry experiments demonstrate that HCMV infection decreases cell-surface MHC class II expression. HCMV down-regulates MHC class II surface expression without a significant effect on class II RNA or steady-state protein levels. SDS-stability and confocal microscopy experiments demonstrate normal levels of steady-state peptide-loaded class II molecules in infected cells and that class II molecules reach late endosomal and HLA-DM positive peptide-loading compartments. However, MHC class II positive vesicles are retained in an abnormal perinuclear distribution. Finally, experiments with a mutant HCMV strain demonstrate that this novel mechanism of decreased MHC class II expression is not mediated by one of the known HCMV immunomodulatory genes. These defects in MHC class II expression combined with previously identified CMV strategies for decreasing MHC class I expression enables infected cells to evade T lymphocyte immunosurveillance.
CD8(+)和CD4(+) T淋巴细胞在控制人巨细胞病毒(HCMV)感染中起重要作用,但该病毒已进化出多种机制来抑制基于MHC的抗原呈递并逃避T淋巴细胞免疫监视。在此,在稳定转染了II类反式激活因子的细胞中研究了HCMV与MHC II类抗原呈递途径的相互作用。流式细胞术实验表明,HCMV感染会降低细胞表面MHC II类分子的表达。HCMV下调MHC II类分子的表面表达,但对II类RNA或稳态蛋白水平无显著影响。SDS稳定性和共聚焦显微镜实验表明,感染细胞中稳态肽负载的II类分子水平正常,且II类分子可到达晚期内体和HLA-DM阳性肽负载区室。然而,MHC II类阳性囊泡保留在异常的核周分布中。最后,用突变的HCMV毒株进行的实验表明,这种降低MHC II类分子表达的新机制不是由已知的HCMV免疫调节基因之一介导的。MHC II类分子表达的这些缺陷与先前确定的CMV降低MHC I类分子表达的策略相结合,使感染细胞能够逃避T淋巴细胞免疫监视。