This proposal will extend work in three main areas: 1) pathogenesis of acute rheumatic fever and its possible relationship to B-cell alloantigens defined by two recently-developed mouse monoclonal antibodies 883 and 256; 2) studies of antiidiotypic control mechanisms influencing anti-ds-DNA antibody production during the course of systemic lupus erythematosus (SLE); and 3) further investigations concerning immunochemical specificity and possible physiologic significance of anti-lymphocyte antibodies in patients with SLE. The work directed at possible B-cell alloantigen control of host immune response to group A streptococcal antigens will attempt to provide better immunochemical definition of the B-cell surface components reacting with the 883 and 256 reagents. In addition, comparative in vitro assays are planned using various streptococcal and control antigens in experiments using peripheral blood and mononuclear cell stimulation and macrophage pulsing with 883/256 (+) and (-) donors. Studies of anti-idiotypic control mechanisms in SLE will utilize monoclonal murine antibodies produced against a panel of isolated SLE anti-ds-DNA antibodies as well as radioimmunoassay and ELISA techniques to define auto-anti-DNA idiotypic reactions. The possibility that antibodies showing anti-F(ab')2 specificity may be representative of a broad pool of anti-idiotypes some of which are enriched for antids-DNA anti-idiotypic reactivity will be sequentially explored using affinity column purified anti-DNA and anti-F(ab')2 antibodies and ELISA assay techniques. Finally, specific studies of lymphocyte glycoproteins reacting with anti-lymphocyte antibodies from SLE will be performed using lymphocyte cell membrane proteins separated by SDS PAGE gels and transferred to nitrocellulose paper. Further definition of the mechanisms whereby IgG antibodies from SLE serum are capable of penetrating living cells will be performed using sequential electronmicroscope monitoring.
