STUDIES OF AUTOANTIBODIES AND IMMUNOGLOBULINS

这项建议将在三个主要领域扩展工作：1)发病机制 急性风湿热及其与B细胞同种异体抗原的可能关系 由两个最近开发的鼠单抗883和256定义； 2)影响抗ds-DNA的抗独特型调控机制的研究 系统性红斑狼疮病程中抗体的产生 (SLE)；以及3)关于免疫化学特异性的进一步研究 抗淋巴细胞抗体可能的生理意义 SLE患者。这项工作是针对可能的B细胞同种异体抗原 控制宿主对A组链球菌抗原的免疫反应将 尝试为B细胞表面提供更好的免疫化学定义 与883和256试剂反应的成分。此外, 计划使用不同的链球菌和 用外周血和单个核细胞控制实验中的抗原 883/256(+)和(-)供者的刺激和巨噬细胞搏动。 系统性红斑狼疮抗独特型调控机制的研究将利用单抗 针对一组分离的SLE抗ds-DNA产生的小鼠抗体 抗体以及放射免疫分析和酶联免疫吸附试验技术 自身抗DNA独特型反应。抗体有可能显示出 抗F(ab‘)2特异性可能代表广泛的 抗独特型，其中一些富含抗ds-DNA抗独特型 将使用纯化的亲和层析柱顺序探索反应性 抗DNA和抗F(ab‘)2抗体及酶联免疫吸附试验技术。最后， 淋巴细胞糖蛋白与抗淋巴细胞反应的特异性研究 来自SLE的抗体将使用淋巴细胞膜进行检测 用十二烷基硫酸钠-PAGE凝胶分离蛋白质并转移到硝化纤维 纸。进一步定义免疫球蛋白抗体从 能够穿透活细胞的SLE血清将使用 顺序电子显微镜监测。

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.