The AIDS pandemic has dramatically shown that retroviruses cause significant disease in man as well as various animal species as has been appreciated for several decades. In spite of the rapid identification of the HIV's as the causative retrovirus in AIDS and a tremendous amount of detailed information characterizing HIV at a molecular level, there are still major gaps in the understanding of AIDS pathogenesis and how these retroviruses interact with the immune system. Part of the difficulty in answering these latter questions has stemmed from the lack of availability of a small animal model system for AIDS. In this proposal a relatively new mouse model system of retrovirus-induced immunodeficiency initiated by the LP-BM5 viral isolate is utilized to ask several key and fundamental questions about how T lymphocytes, especially cytolytic T lymphocytes (CTL), recognize the causative retroviruses and what effect such recognition has on the disease process. Although not a lentivirus like HIV, LP-BM5 induces a spectrum of disease features similar to AIDS including severe immunosuppression of both B and T lymphocyte responses, dependence of the initiation of the disease on CD4+ T lymphocytes, polyclonal B cell activation and hypergammaglobulinemia, lymphadenopathy, increased susceptibility to progressive infections by environmental pathogens that cause only inapparent infections in normal individuals, and an increased incidence of B cell lymphomas in the terminal stages of immunodeficiency. For these reasons LP-BM5 induced disease has been termed mouse AIDS (MAIDS). In this proposal CTL that have already been generated to the retroviral gag gene product of the LP-BM5 defective retrovirus, the proximal etiologic agent of MAIDS, or to MAIDS-associated B cell lymphomas will be further characterized as to their epitope specificity and compared directly in Fl mice for their ability to protect from, or conversely to possibly enhance, LP-BM5 induced immunodeficiency. Attempts will also be made to generate CTL to the helper retrovirus in LP-BM5 necessary for packaging the defective retroviral genome. If such responses are obtained, their functional relevance will also be determined. The ability to raise gag-, helper virus-, and MAIDS tumor-specific CTL in selected mouse strains either genetically susceptible or resistant to MAIDS will also be examined. In this way it is hoped that general information will be obtained on the specific recognition of LP-BM5 retroviruses by T cells and the interaction of these viruses with the immune system, and that such findings will not only help in the understanding of MAIDS but have implications for AIDS.
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