Section of Hepatology, Department of Medicine, University of Illinois at Chicago, Illinois, USA.
Virol J. 2011 Jul 29;8:377. doi: 10.1186/1743-422X-8-377.
Antigenic variation is an effective way by which viruses evade host immune defense leading to viral persistence. Little is known about the inhibitory mechanisms of viral variants on CD4 T cell functions.
Using sythetic peptides of a HLA-DRB115-restricted CD4 epitope derived from the non-structural (NS) 3 protein of hepatitis C virus (HCV) and its antigenic variants and the peripheral blood mononuclear cells (PBMC) from six HLA-DRB115-positive patients chronically infected with HCV and 3 healthy subjects, the in vitro immune responses and the phenotypes of CD4+CD25+ cells of chronic HCV infection were investigated. The variants resulting from single or double amino acid substitutions at the center of the core region of the Th1 peptide not only induce failed T cell activation but also simultaneously up-regulate inhibitory IL-10, CD25-TGF-β+ Th3 and CD4+IL-10+ Tr1 cells. In contrast, other variants promote differentiation of CD25+TGF-β+ Th3 suppressors that attenuate T cell proliferation.
Naturally occuring HCV antigenic mutants of a CD4 epitope can shift a protective peripheral Th1 immune response into an inhibitory Th3 and/or Tr1 response. The modulation of antigenic variants on CD4 response is efficient and extensive, and is likely critical in viral persistence in HCV infection.
抗原变异是病毒逃避宿主免疫防御从而导致病毒持续存在的有效方式。目前对于病毒变异对 CD4 T 细胞功能的抑制机制知之甚少。
我们使用源自丙型肝炎病毒（HCV）非结构（NS）3 蛋白的 HLA-DRB115 限制性 CD4 表位的合成肽及其抗原变异体以及来自 6 名慢性 HCV 感染的 HLA-DRB115 阳性患者和 3 名健康受试者的外周血单个核细胞（PBMC），研究了慢性 HCV 感染的体外免疫反应和 CD4+CD25+细胞表型。在 Th1 肽核心区域的单个或双氨基酸取代导致的变异不仅诱导 T 细胞激活失败，而且同时上调抑制性 IL-10、CD25-TGF-β+Th3 和 CD4+IL-10+Tr1 细胞。相比之下，其他变异体促进 CD25+TGF-β+Th3 抑制物的分化，从而减弱 T 细胞增殖。
自然发生的 HCV 抗原突变体可将保护性外周 Th1 免疫反应转变为抑制性 Th3 和/或 Tr1 反应。抗原变异体对 CD4 反应的调节是高效和广泛的，这可能是 HCV 感染中病毒持续存在的关键因素。
