MECHANISMS OF THE H-2 EFFECT ON VIRAL LEUKEMOGENESIS

最近发现了会导致人类患病的逆转录病毒。 由于我们对这些病毒的免疫反应的了解，特别是 细胞免疫反应，是初级的，研究势在必行 模型系统中对逆转录病毒的免疫力。以此为基础的研究 GRANT旨在阐明细胞免疫反应在 小鼠对构成Friend红白血病病毒的逆转录病毒的反应 复合体(Fv)。我们已经开发出一种系统，在该系统中，个体分子 该复合体的克隆病毒(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细胞中表达。当适当的时候小鼠 I类主要组织相容性分子也被引入到每个 细胞系，该细胞成为细胞毒T淋巴细胞的潜在靶点 (CTL)用感染该病毒的细胞免疫小鼠而产生 FV复合体的分子克隆病毒。三种不同的犯罪模式分析 不同CTL群体对不同合成靶点的反应性 LINE将识别目标中涉及的病毒组件 CTL识别的结构。我们还将确定特定的地区 构建CTL识别表位的病毒基因 用于分析突变的病毒基因。我们将构建一个包装不足的 FV复合体辅助成分的突变以产生病毒 不含RNA的颗粒用于研究其免疫抗病毒的能力 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.