The mechanism of thymic leukemia will be studied in HRS/J and AKR mice, with particular emphasis on virological and immunological factors. We will test the hypothesis that each cloned leukemogenic virus induces a corresponding clone of neoplastic cells with a unique, virus-specific array of differentiation antigens. Another hypothesis we will test is that spontaneous and induced leukemias possess surface receptors that bind specifically to the recombinant virus that caused the leukemia. The nature of the virus-specific binding structure on leukemic cells will be characterized by means of monoclonal antibodies and anti-idiotypic antibodies. An in vitro system to analyze viral leukemogenesis will be developed using technics of T cell culture. We will survey the genomes and proviruses of endogenous ecotropic, xenotropic, and polytropic viruses of HRS?J, AKR, amd NZB mice in order to establish relationships among these viruses and to associate specific viruses with specific endogenous proviruses. The non-ecoptropic parental proviruses that give rise to the substituted regions of polytropic viruses will be characterized. Specific integrations of proviruses and altered virus-related transcripts will be sought in leukemic cells.