NUCLEAR PROTEINS AND AUTOIMMUNITY

抗核抗体是自身免疫性疾病的标志。 这项研究是针对表征的 作为各种风湿性关节炎指标的核蛋白 系统性红斑狼疮（SLE）和混合性红斑狼疮 结缔组织病（MCTD）。 两种这样的抗原已经被 命名为Sm和RNP。 这些抗原共同代表 至少有10种多肽，所有这些多肽都是 snRNP（small nuclear ribonucleoprotein）。 这些抗原的表征将涵盖从 免疫反应性多肽与组成snRNP复合物的结合。 重点放在单个多肽上，以将它们用作 制定具体和定量的 Sm和RNP抗体的诊断/预后测定。 到 为此，本实验室的一个主要持续重点是使用 用于cDNA克隆的重组DNA技术， 相关抗原的表达。 cDNA的可用性 克隆和重组多肽也将允许关键的 多种Sm和RNP多肽在不同水平的评估 以帮助描绘抗原和snRNP结构。 这些研究将包括在基因组水平上： 密切相关的多肽;北方印迹分析， 表征特定的mRNA种类;对完整的 基因 详细的抗原分析将通过以下方式进行： 作图;在肽和 基因组（Southern印迹分析）水平;探索可能的 这些抗原和感染因子之间的关系。 研究将继续对snRNP复合物与 这些抗原，特别强调分离 单个snRNP颗粒，以及蛋白质-蛋白质 和蛋白质-RNA相互作用;所有这些都将提供 关于功能性颗粒的组装的信息。 一 这些研究的必然结果是， 单克隆和多克隆抗体 probes. 最后，这些研究将扩大到包括其他 与自身免疫抗原同义的核蛋白， 特别是hnRNP和核基质蛋白。 总的来说这些 研究正在询问是什么特征使抗原如Sm和 RNP靶点在自身免疫性事件序列中， 将这些相同的多肽释放到天然细胞环境中， 它们的功能。

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 (SLE) and mixed connective tissue disease (MCTD). Two such antigens have been designated Sm and RNP. Together these antigens are represented by at least 10 polypeptides, all of which are part of larger particles called the snRNP (small nuclear ribonucleoprotein). Characterization of these antigens will cover the spectrum from immunoreactive polypeptide to constituent snRNP complexes. Emphasis is being placed on individual polypeptides to use them as the basis for the development of specific and quantitative diagnostic/prognostic assays for the Sm and RNP antibodies. To that end a major continuing emphasis in this laboratory is the use of recombinant DNA technology for the cDNA cloning and expression of the relevant antigens. The availability of cDNA clones and recombinant polypeptides will also allow for a critical assessment of multiple Sm and RNP polypeptides at various levels to aid in the delineation of both antigen and snRNP structure. These studies will include at the genomic level: discrimination of closely related polypeptides; Northern blot analyses to characterize specific mRNA species; sequencing of the intact gene. Detailed antigen analysis will be facilitated by: epitope mapping; interspecies comparisons at both the peptide and genomic (Southern blot analysis) levels; exploration of possible relationships between these antigens and infectious agents. Studies will continue on the snRNP complexes associated with these antigens, with particular emphasis on the isolation of individual snRNP particles, as well as studies of protein-protein and protein-RNA interactions; all of which will provide information as to the assembly of the functional particle. A corollary to these studies is the continued production of monoclonal and polyclonal antibodies with utility as molecular probes. Lastly these studies will be expanded to include other nuclear proteins synonymous with autoimmune antigens, in particular hnRNP and nuclear matrix proteins. Overall these studies are asking what features make antigens such as Sm and RNP targets in the autoimmune sequence of events, while relating these same polypeptides to the native cellular environment in which they function.