NUCLEAR PROTEINS AND AUTOIMMUNITY

抗核抗体是自身免疫性疾病的标志。 这项研究的目的是为了描述 核蛋白可作为各种风湿病的指标 疾病，包括系统性红斑狼疮(SLE)和混合性 结缔组织病(MCTD)。已经有两种这样的抗原 指定为Sm和RNP。这些抗原一起代表 由至少10个多肽组成，所有这些多肽都是更大的 被称为SnRNP(小核核糖核蛋白)的颗粒。 对这些抗原的表征将涵盖来自 对组成SNRNP复合体的免疫反应性多肽。 重点放在单个多肽上，以将它们用作 发展的基础是具体的和定量的 Sm和RNP抗体的诊断/预后分析。至 为此，本实验室继续强调的一个主要方面是使用 重组DNA技术用于cDNA克隆和 相关抗原的表达。基因的可获得性 克隆和重组多肽也将允许关键的 多种Sm和RNP多肽在不同水平上的评价 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的歧视 紧密相关的多肽；Northern印迹分析 确定特定的信使核糖核酸的种类；完整的序列 吉恩。详细的抗原分析将由：表位提供便利 测绘；多肽和蛋白质的种间比较 基因组(Southern杂交分析)水平；探索可能的 这些抗原与感染性病原体之间的关系。 将继续对与以下各项相关的SNRNP复合体进行研究 这些抗原，特别强调分离 单个SnRNP颗粒以及对蛋白质-蛋白质的研究 和蛋白质-RNA相互作用；所有这些都将提供 关于功能粒子的组装的信息。一个 这些研究的必然结果是继续产生 用作分子的单抗和多克隆抗体 探测器。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，在 特别是hnRNP和核基质蛋白。总体来说，这些 研究正在询问是什么特征使Sm和Sm等抗原 在自身免疫事件序列中的RNP靶标，同时与 这些相同的多肽对自然细胞环境的影响 它们的功能就是。

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.