STRUCTURE AND FUNCTION OF AN AUTOIMMUNE ANTIGEN

针对核的循环抗体的存在 抗原是许多系统性风湿病的共同症状。 疾病。许多系统性红斑狼疮(SLE)患者 产生与丰富的小核相互作用的抗体 真核细胞中发现的核糖核蛋白复合体(SnRNPs)。 一类能沉淀SNRNPs的自身免疫血清 含有小核RNA U1、U2、U4、U5和U6的是 叫做反Sm。由于抗Sm抗体的产生很少 由患有其他结缔组织疾病的患者发现 这种特异性可作为SLE的一个有用的血清学标志物。 抗Sm血清识别的蛋白质之一是11,000 道尔顿“E”蛋白。这种蛋白质是所有抗- SM反应性SNRNP，但对其结构或功能知之甚少 功能。我们计划使用我们最近分离的cdna克隆来 E蛋白来表征这种自身免疫抗原的基因， 并研究该蛋白在细胞生理学中的作用。 最后，我们计划利用蛋白质的结构信息 通过对E蛋白基因进行测序获得 这个蛋白质的一部分实际上是被抗Sm识别的 抗体。 这些研究不仅应该增进我们对 自身免疫性疾病的病因学，但应该有助于我们设计一种 克隆和分析相关Sm基因的合理策略 抗原。

The presence of circulating antibodies directed against nuclear antigens is a common symptom to many systemic rheumatic diseases. Many patients with systemic lupus erythematosus (SLE) produce antibodies which interact with abundant small nuclear ribonucleoprotein complexes (snRNPs) found in eukaryotic cells. The class of autoimmune sera which precipitate snRNPs containing the small nuclear RNAs U1, U2, U4, U5 and U6 is called anti-Sm. Since anti-Sm antibodies are only rarely produced by patients with other connective tissue diseases, the presence of this specificity serves as a useful serological marker for SLE. One of the proteins recognized by anti-Sm sera is the 11,000 dalton "E" protein. This protein is a component of all of the anti- Sm reactive snRNPs, but little is known about its structure or function. We plan to use our recently isolated cDNA clone for the E protein to characterize the genes for this autoimmune antigen, and to investigate the role of this protein in cellular physiology. Finally we plan to exploit the protein structural information obtained from sequencing the E protein gene to determine which portion of this protein is actually recognized by anti-Sm antibodies. These studies should not only enhance our understanding of the etiology of autoimmune disease, but should help us design a rational strategy for the cloning and analysis of related Sm antigens.