MECHANISMS OF THE H-2 EFFECT ON VIRAL LEUKEMOGENESIS

最近已经鉴定出在人类中引起疾病的逆转录病毒。 自从我们了解了对这些病毒的免疫反应， 细胞免疫反应，是基本的，这是必要的研究 在模型系统中对逆转录病毒的免疫。 这项研究支持的是 格兰特是针对阐明细胞免疫反应， 小鼠的逆转录病毒，包括朋友红白血病病毒 复合物（FV）。 我们开发了一个系统， 该复合物的克隆病毒（F-MuLV、SFFV和F-MCF），以及 每种病毒的单个分子克隆基因，可以被引入到 并在大鼠成纤维细胞系的细胞中表达。 适当时，鼠 I类主要组织相容性分子也被引入到每个细胞中， 细胞系，细胞成为细胞毒性T淋巴细胞的潜在靶 (CTL)通过用被其感染的细胞免疫小鼠而产生 FV复合物的分子克隆病毒。 分析的模式 不同CTL群体对不同“合成”靶标的反应性 线将确定涉及目标的病毒的组成部分 CTL识别的结构。 我们还将确定特定区域 通过构建编码CTL识别表位的病毒基因， 用于分析的突变病毒基因。 我们将构建一个包装缺陷 FV复合体辅助成分的突变体，以产生病毒 不含RNA的颗粒，用于研究其免疫抗 传染性病毒

Retroviruses that cause disease in humans have been identified recently. Since our understanding of immune response to these viruses, especially cellular immune responses, is rudimentary, it is imperative to study immunity to retroviruses in model systems. The studies supported by this grant are directed toward elucidation of the cellular immune response in mice to the retroviruses that comprise the Friend erythroleukemia virus complex (FV). We have developed a system in which individual molecularly cloned viruses of this complex (F-MuLV, SFFV and F-MCF), as well as individual molecularly cloned genes of each virus, can be introduced into and expressed in cells of a rat fibroblast line. When appropriate murine class I major histocompatibility molecules are also introduced into each cell line, the cells become potential targets for cytotoxic T lymphocytes (CTL) generated by immunizing mice with cells infected by the same molecularly cloned viruses of the FV complex. Analysis of the patterns of reactivity of different CTL populations on different "synthetic" target lines will identify the components of the virus involved in target structures recognized by the CTL. We will also identify particular regions of the viral genes encoding epitopes for CTL recognition by constructing mutant viral genes for analysis. We will construct a packaging-deficient mutant of the helper component of FV complex in order to produce virus particles free of RNA for studies of their capacity to immunize against infectious virus.