A variety of immunologic abnormalities have been associated with human T-lymphotropic/lymphadenopathy virus (HTLV-III/LAV) infections which are a hallmark of acquired immunodeficiency syndrome (AIDS). Factors which contribute to this immunosuppression are the focus of this proposal. Specifically, studies in our laboratory have demonstrated homologous sequences between the HTLV-III/LAV envelope protein and interleukin-2 (IL-2). The presence of such sequences suggested to us that in the course of mounting an antibody response against HTLV-III/LAV, crossreacting anti-IL-2 antibodies might be generated. Initial studies in our laboratory have demonstrated that in fact some AIDS patients have circulating antibodies against IL-2. Since IL-2 is necessary for immune competence, it is probable that these antibodies contribute to the immune suppression seen in AIDS. The purpose of this proposal is to characterize the anti-IL-2 antibodies and subsequently quantitating the amount of specific antibody using standard enzyme linked immunosorbent assays (ELISAs) or radioimmunoassays (RIA). We are also interested in correlating antibody levels with the severity of the disease. Characteristics of the anti-IL-2 antibody response will be carried out by isolating the specific antibodies on affinity columns. This will allow us to determine the particular immunoglobulin isotype and how the antibodies neutralize IL-2 biological activity. Mice will be immunized with IL-2 to see if an AIDS-like immunosuppression is observed. Finally, anti-idiotypic antibodies directed against the anti-IL-2 antibodies will be characterized for their ability to bind the IL-2 receptor. Overall, we anticipate that these studies will help to define one specific factor involved in HTLV-III/LAV- induced immunosuppression, namely the production of anti-IL-2 antibodies.
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