NUCLEAR PROTEINS AND AUTOIMMUNITY

抗核抗体是自身免疫性疾病的标志。这项研究 针对的是核蛋白的特性 作为各种风湿性疾病的指标，包括系统性红斑狼疮 红斑症和干燥综合征。两种这样的抗原被命名为Sm 和RNP；两者都与一类保守的蛋白质有关 被称为SNRNP(小核核糖核蛋白)。我们已经确定了 Sm和RNP免疫活性多肽及证明抗Sm 多肽可以可靠地区分抗RNP血清 每个人都能认出。我们现在建议将这些多肽的特征描述为 其独特的物理化学和RNA结合特性，并将其用作 我们开发Sm的特异性和定量分析的基础 和RNP抗体。将这两种抗原与它们的功能联系起来 细胞环境，我们还将描述它们的特征，因为它们存在于SnRNP中 与它们各自的RNA物种相关联，相互关联，并与 其他蛋白质。干燥综合征相关的La或SS-B抗原 也以核糖核蛋白复合体的形式存在，其特征是 类似于Sm和RNP的方式。La抗原是相对于 其他两种抗原作为其相关的RNA物种从未感染的 病毒感染的细胞。因此，La也将被定义为 病毒相关抗原，特别强调其细胞位置 以及受感染细胞的任何物理化学性质的变化。这 鉴定还将包括Ro或SS-A抗原的检查 以及它与洛杉矶的关系。这些研究的一个推论是我们继续 主要通过使用小鼠产生单特异性抗体 杂交瘤。所有这些研究都将扩展到 其他具有诊断潜力的核抗原的鉴定 西方印迹技术已被证明是一种如此强大的工具 鉴定Sm、RNP和La免疫活性物种。最后，我们打算 Sm、RNP和La免疫活性多肽编码基因的克隆 从人类的cdna文库中提取。总体而言，确定的抗原的可用性 它们相应的抗体应该允许发展成 各种风湿性疾病的标准化诊断测试，并帮助 来描述这些蛋白质在自身免疫反应中的作用。

Antinuclear antibodies are a hallmark of autoimmune disease. This research is directed toward the characterization of the nuclear proteins that serve as indicators of various rheumatic diseases, including systemic lupus erythematosus and Sjogren's Syndrome. Two such antigens are designated Sm and RNP; both have been associated with a conserved class of proteins called the snRNP (small nuclear ribonucleoproteins). We have identified the Sm and RNP immunoreactive polypeptides and demonstrated that anti-Sm and anti-RNP sera may be reliably distinguished by the polypeptides recognized by each. We now propose to characterize these polypeptides as to their unique physicochemical and RNA-binding properties, and use them as the basis for our development of specific and quantitative assays for Sm and RNP antibodies. To relate these two antigens to their functional cellular environment, we will also characterize them as they exist in snRNP in association with their respective RNA species, with each other, and with other proteins. The La or SS-B antigen associated with Sjogren's Syndrome also exists as a ribonucleoprotein complex and will be characterized in a manner analogous to Sm and RNP. The La antigen is unique relative to the other two antigens as its associated RNA species change from a noninfected to a virus infected cell. Thus La will also be defined as a virus-associated antigen with particular emphasis on its cellular location and any change in physicochemical properties in the infected cell. This characterization will also include an examination of the Ro or SS-A antigen and its relationship to La. A corollary to these studies is our continued production of monospecific antibodies primarily through the use of mouse hybridomas. All of these studies are to be expanded toward the identification of other nuclear antigens with diagnostic potential using the Western blot technique which has proved to be such a powerful tool in identifying the Sm, RNP and La immunoreactive species. Lastly, we intend to clone the genes encoding the Sm, RNP and La immunoreactive polypeptides from a human cDNA library. Overall, the availability of defined antigens and their corresponding antibodies should permit the development of standardized diagnostic tests for a variety of rheumatic diseases, and help to delineate the role of these proteins in the autoimmune response.