MECHANISMS OF THE H-2 EFFECT ON VIRAL LEUKEMOGENESIS

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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.