T CELL RECEPTORS AND ANTI-RO/SSA ANTIBODY PRODUCTION

T 细胞受体和抗 RO/SSA 抗体生产

• 批准号: 3809934
• 负责人: MARK BARTON FRANK
• 金额: --
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3809934
• 关键词: Sjogren's syndrome; T cell receptor; autoantibody; autoantigens; autoimmune disorder; enzyme linked immunosorbent assay; gene expression; genetic library; genetic markers; human tissue; molecular cloning; nucleic acid probes; restriction fragment length polymorphism; ribonucleoproteins; systemic lupus erythematosus

Serum autoantibodies are a characteristic of patients with systemic lupus erythematosus. Some of these bind to the ribonucleoprotein complexes Ro/SSA and La/SSB. Strong associations between the presence of these autoantibodies and particular HLA class II molecules have been described. The biological function of these HLA molecules suggests that specific T cell receptors may recognize Ro/SSA-HLA and La/SSB-HLA complexes and play a critical in the perpetuation of these autoimmune responses. Polymorphisms of the T cell receptor beta genes have been identified by the principal investigator which act as genotypic markers for the subset of lupus patients which produce anti=Ro/SSA autoantibodies, and which are strongly associated with HLA genetic markers. In this study, the molecular characteristics of these T cell receptor genes will be elucidated. Variable genes which code for Ro/SSA-specific T cell receptors will be isolated by subtractive DNA techniques and sequenced. The germline sequences of diversifying and joining genes will also be determined and compared between patients with and without the anti-Ro/SSA antibody. T cells selected for the recognition of the Ro/SSA molecule will be cloned, and cDNA of their T cell receptor transcripts produced. Nucleotide sequencing of these molecules will determine if the genes identified above are expressed as functional T cell receptors in Ro/SSA-responsive cells. The genes identified in these experiments will be used as nucleotide probes to study the familial response to Ro/SSA and the role that similar T cell receptors may play in the anti-Ro/SSA immune response in Sjogren's syndrome patients. These studies will enhance our basic knowledge of T cell receptors and their role in autoimmunity. They will be useful in understanding multigenic interaction in the immune response, and may be of use in the future in designing immunomodulatory regimens in lupus patients.

血清自身抗体是系统性狼疮患者的一个特征 红斑狼疮。 其中一些与核糖核蛋白复合物结合 Ro/SSA 和 La/SSB。 这些的存在之间存在很强的关联 自身抗体和特定的 HLA II 类分子已被描述。 这些 HLA 分子的生物学功能表明，特定的 T 细胞受体可能识别 Ro/SSA-HLA 和 La/SSB-HLA 复合物并发挥作用 对于这些自身免疫反应的持续发挥至关重要。 多态性 T 细胞受体 β 基因的主要研究人员已鉴定出 作为狼疮子集基因型标记的研究者 产生抗 Ro/SSA 自身抗体且强烈 与 HLA 遗传标记相关。 在这项研究中，分子 这些T细胞受体基因的特征将得到阐明。 编码Ro/SSA特异性T细胞受体的可变基因将是 通过消减DNA技术分离并测序。 种系 多样化和连接基因的序列也将被确定并 比较有和没有抗Ro/SSA抗体的患者。 时间 选择识别 Ro/SSA 分子的细胞将被克隆， 以及产生的 T 细胞受体转录本的 cDNA。 核苷酸 这些分子的测序将确定上面确定的基因是否 在 Ro/SSA 反应细胞中表达为功能性 T 细胞受体。 这些实验中鉴定的基因将用作核苷酸探针 研究 Ro/SSA 的家族反应以及类似 T 细胞的作用 受体可能在干燥综合征的抗 Ro/SSA 免疫反应中发挥作用 患者。 这些研究将增强我们对T细胞的基础知识 受体及其在自身免疫中的作用。 它们将在以下方面有用： 了解免疫反应中的多基因相互作用，并且可能是 未来用于设计狼疮患者的免疫调节方案。