Kowalski H, Erickson A L, Cooper S, Domena J D, Parham P, Walker C M
Department of Structural Biology, Stanford University, California 94305, USA.
J Exp Med. 1996 Apr 1;183(4):1761-75. doi: 10.1084/jem.183.4.1761.
Common chimpanzees (Pan troglodytes) infected with hepatitis C virus (HCV) show a disease progression similar to that observed for human patients. Although most infected animals develop a chronic hepatitis, virus persistence is associated with an ongoing immune response, for which the beneficial or detrimental effects are uncertain. Lines of virus-specific cytotoxic CD8+ T lymphocytes (CTL) have been previously established from liver biopsies of two common chimpanzees chronically infected with HCV-1. The viral epitopes recognized by six lines of CTL have been defined using synthetic peptides and shown to consist of 8 to 9-residue peptides derived from various viral proteins. Five of the epitopes derive from sequences that vary among strains of HCV. The majority of the corresponding variant epitopes from different HCV strains were either recognized less efficiently or not at all by the CTL, suggesting their response may have limited potential for controlling replication of HCV variants. Complementary DNAs encoding class I alleles of the two common chimpanzees, Patr-A, -B, and -C were cloned, sequenced, and transfected individually into a class I-deficient human cell line. Analysis of peptide presentation by the class I transfectants to CTL identified the Patr class I allotypes that present the six epitopes defined here and an additional epitope defined previously. The assignment of epitopes to class I allotypes based upon analysis of the transfected cells correlates precisely with the segregation of antigen-presenting function within a panel of common chimpanzee cell lines and the expression of class I heavy chains as defined by isoelectric focusing. Five of the HCV-1 epitopes are presented by Patr-B allotypes, two epitopes are presented by a Patr-A allotype, and none is presented by Patr-C allotypes.
感染丙型肝炎病毒（HCV）的普通黑猩猩（Pan troglodytes）表现出与人类患者相似的疾病进展。尽管大多数受感染动物会发展为慢性肝炎，但病毒持续存在与持续的免疫反应相关，而这种免疫反应的有益或有害影响尚不确定。此前已从两只慢性感染HCV-1的普通黑猩猩的肝活检组织中建立了病毒特异性细胞毒性CD8 + T淋巴细胞（CTL）系。已使用合成肽确定了六株CTL识别的病毒表位，并显示其由源自各种病毒蛋白的8至9个残基的肽组成。其中五个表位来自HCV不同毒株间存在差异的序列。来自不同HCV毒株的大多数相应变异表位被CTL识别的效率较低或根本不被识别，这表明它们的反应在控制HCV变异体复制方面的潜力可能有限。对这两只普通黑猩猩的I类等位基因Patr-A、-B和-C的互补DNA进行了克隆、测序，并分别转染到一个I类缺陷的人类细胞系中。通过I类转染体向CTL呈递肽的分析，确定了呈递此处定义的六个表位和先前定义的另一个表位的Patr I类同种异型。基于对转染细胞的分析将表位分配给I类同种异型，这与一组普通黑猩猩细胞系中抗原呈递功能的分离以及通过等电聚焦定义的I类重链的表达精确相关。五个HCV-1表位由Patr-B同种异型呈递，两个表位由Patr-A同种异型呈递，没有一个表位由Patr-C同种异型呈递。
