This is a continuation of our study of the receptor-mediated leukemogenesis hypothesis. The receptor mediated leukemogenesis hypothesis was, I believe, the first oncogenesis model wherein cell surface receptors involved in the triggering of cell division in normal cells would be utilized for unregulated cell division in neoplastic cells. In the particular case we have proposed, immunospecific antigen receptors on T and B cell lymphomas are proposed as binding and growth stimulating sites by the oncogenic retrovirus they produce. We have recently demonstrated that an immunoglobulin receptor on a B cell lymphoma (BCL-1) and the T cell antigen receptor on a T cell lymphoma (C6VL) are at or near retrovirus binding sites on these lymphomas. In addition, we have demonstrated specific binding of the human T cell leukemia virus (HTLV) on several HTLV induced human T cell leukemias/cell lines. During this next grant period we propose to investigate whether the retrovirus receptors on these lymphomas is indeed at, rather than near, the antigen receptors on mouse and human T cell leukemias/lymphomas. In addition, we shall test the consequences of retrovirus binding to these lymphomas in terms of activation of intracellular mediators of mitogenesis. Finally, utilizing recombinant DNA techniques we hope to transfect and express T cell receptor genes from these lymphomas into cell which will produce and secrete the receptors for detailed analysis of their antigen specificity. In summary, this is the continuation of the study of the pathogenesis of RNA tumor virus induced leukemias and lymphomas. During this next grant interval we shall extend our studies to samples from a human disease, the current epidemic of adult-onset, rapidly lethal, HTLV induced leukemias and lymphomas. Because the virus used for these studies - HTLV-1 - is closely related to another virus - HTLV-3 - which eliminates rather than neoplastically transforming lymphocytes, it is conceivable that an understanding of target receptors for these viruses might lead to an approach to AIDS.
