Green W R, Brown M A
Eur J Immunol. 1983 Nov;13(11):871-7. doi: 10.1002/eji.1830131103.
Derived from the susceptible AKR.H-2bSL1 tumor cell line, a variant tumor subclone, cl.18-5, was selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL) due to its failure to be recognized. In this study, the expression of virus-related products by variant cl.18-5 cells was compared to that of AKR.H-2bSL1 cells and a susceptible clone, as an approach towards defining the virus-associated antigens recognized by anti-AKR/Gross virus CTL. Despite the type specificity of the CTL, cl.18-5 displayed normal levels of the group-specific antigen (gag) encoded proteins p30, p15, p12 and p10, and the gag-associated Gross cell surface antigen. These results were confirmed by fluorescence-activated cell sorter analysis employing monoclonal antibodies specific for either AKR p12 or the cell surface glycosylated form of AKR ecotropic gag product. In contrast, cl.18-5 was variably less sensitive than AKR.H-2bSL1 to the action of complement and xenogeneic antisera directed against the envelope (env) product gp70. In addition, a panel of five monoclonal antibodies to gp70, which detect distinct endogenous ecotropic viral determinants, lysed AKR.H-2bSL1, but not cl.18-5 cells. However, absorption experiments indicated that cl.18-5 did express near normal levels of these specificities, suggesting an alteration in the orientation or topographical distribution of these determinants. Consistent with an inappropriate display of env products, cl.18-5 was found to be deficient in the production of infectious ecotropic leukemia virus. The particulate fraction of the cell-free supernatant of cl.18-5 contained normal levels of reverse transcriptase activity, indicating that noninfectious viral particles were being produced. Collectively, these results point to an association between recognition by anti-AKR/Gross virus CTL and the expression of ecotropic gp70 required for infectivity of virus.
源自敏感的AKR.H-2bSL1肿瘤细胞系的一个变异肿瘤亚克隆cl.18-5，因其无法被识别而对H-2限制的抗AKR/格罗斯病毒细胞毒性T淋巴细胞（CTL）具有选择性抗性。在本研究中，将变异的cl.18-5细胞与AKR.H-2bSL1细胞及一个敏感克隆的病毒相关产物表达进行了比较，以此作为确定抗AKR/格罗斯病毒CTL所识别的病毒相关抗原的一种方法。尽管CTL具有类型特异性，但cl.18-5显示出正常水平的由群特异性抗原（gag）编码的蛋白质p30、p15、p12和p10，以及与gag相关的格罗斯细胞表面抗原。使用对AKR p12或AKR嗜亲性gag产物的细胞表面糖基化形式具有特异性的单克隆抗体进行的荧光激活细胞分选分析证实了这些结果。相比之下，cl.18-5对针对包膜（env）产物gp70的补体和异种抗血清的作用，其敏感性比AKR.H-2bSL1有不同程度的降低。此外，一组针对gp70的五种单克隆抗体，它们可检测不同的内源性嗜亲性病毒决定簇，能裂解AKR.H-2bSL1细胞，但不能裂解cl.18-5细胞。然而，吸收实验表明cl.18-5确实表达了接近正常水平的这些特异性，这表明这些决定簇的方向或拓扑分布发生了改变。与env产物的不适当展示一致，发现cl.18-5在感染性嗜亲性白血病病毒的产生方面存在缺陷。cl.18-5无细胞上清液的颗粒部分含有正常水平的逆转录酶活性，表明正在产生非感染性病毒颗粒。总体而言，这些结果表明抗AKR/格罗斯病毒CTL的识别与病毒感染性所需的嗜亲性gp70的表达之间存在关联。
