IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

我们的长期目标是了解系统性红斑狼疮的病因 红斑狼疮(SLE)。我们目前的工作试图提供一个全面的 涉及不同抗原-抗体系统的图片 这种疾病患者的核糖核蛋白。其结果是 特定核蛋白，特别是核蛋白的假说的发展 U1SnRNP，核小体，和Ro颗粒，积极地诱导并可能 在这种疾病中传播自身免疫反应。为了发展这一假说 此外，我们现在正集中精力研究该结构和 新发现的自身抗原性Ku蛋白的生物学功能 我们假设染色质成分在DNA修复或 转位--和Ro颗粒--这是自身免疫的中心焦点 系统性红斑狼疮患者的反应。 对Ku蛋白的研究将寻求建立其结构和生物学 功能。我们将使用克隆和标准的生化方法来 鉴定该蛋白的结构并鉴定其自身抗原性 表位。此外，我们还将使用 各种生物检测系统。最后，我们将开发一种新的酶联免疫吸附试验 用于临床研究中抗Ku抗体的检测 Ku蛋白作为抗原。 关于Ro粒子的工作将集中在开发特定的 识别它的探针--包括单抗--设计了一种 体外重组的方法，并确定其在 细胞。此外，我们还将患者血清与免疫动物进行比较 根据各自识别的特定Ro蛋白表位表达的血清。 这项工作将提供关于Ku结构的新信息 蛋白质和Ro粒子。它可能会成功地定义生物学的 这些新发现的细胞元件的功能。有关以下内容的信息 Ku蛋白和Ro颗粒的结构和功能可能有助于 美国理解为什么某些核蛋白成为选定的靶标 系统性红斑狼疮患者的自身免疫反应。

Our long-range objective is to understand the etiology of systemic lupus erythematosus(SLE). Our present work has sought to provide a comprehensive picture of the different antigen-antibody systems that involve ribonucleoproteins in patients with this disease. The outcome has been the development of the hypothesis that specific nucleoproteins, especially the U1 snRNP, the nucleosome, and the Ro particle, actively elicit and possibly propagate autoimmune responses in this disease. To develop this hypothesis further, we are now concentrating our efforts to study the structure and biologic function of the autoantigenic Ku protein--a newly discovered chromatin component which we hypothesize plays a role in DNA repair or transposition--and the Ro particle--which is a central focus of autoimmune responses in patients with SLE. Work on the Ku protein will seek to establish its structure and biologic function. We will use cloning and standard biochemical approaches to characterize this protein structurally and to identify its autoantigenic epitopes. In addition, we will seek to identify its function using a variety of biological assay systems. Finally we will develop a new ELISA for measurement of anti-Ku antibodies in clinical studies using recombinant Ku protein as antigen. Work on the Ro particle will concentrate on developing specific probes--including monoclonal antibodies--that recognize it, devising a method for reconstituting it in vitro, and determining its location in cells. In addition, we will compare patient sera with immunized animal sera in terms of specific Ro protein epitopes recognized by each. This work will provide new information about the structure of the Ku protein and the Ro particle. It may succeed in defining the biological function of these newly recognized cellular elements. Information about the structure and function of the Ku protein and the Ro particle could help us understand why certain nucleoproteins become targets for selected autoimmune responses in patients with SLE.