T-CELL CONTROL OF AUTOREACTIVITY IN SLE

T 细胞对 SLE 自身反应性的控制

• 批准号: 2078942
• 负责人: PHILIP L COHEN
• 金额: $ 20.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2078942
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; antigen presenting cell; autoantibody; autoantigens; autoimmunity; disease /disorder model; genetic markers; genetically modified animals; laboratory mouse; major histocompatibility complex; systemic lupus erythematosus

The proposed studies will focus on the role of the major histocompatibility complex MHC) in the spontaneous systemic autoimmune disease of mice expressing the lpr gene. We have discovered that MHC alleles modify autoimmunity in this murine model. We will take advantage of the many recombinant murine mouse strains to localize the responsible MHC gene or genes. We will utilize unique lpr recombinant mouse strains to ask whether the T-B cell collaboration underlying autoantibody production in this model is restricted by molecules of the MHC. Recent technology makes it possible to identify peptides of processed antigen associated with surface MHC molecules. We will isolate class II MHC molecules from lpr mice and determine the peptides with which they are associated. These studies are expected to yield clues to the nature of T-cell recognition of autoantigens. We will also determine the peptides which result from the processing of known autoantigens by antigen presenting cells of normal and autoimmune mice. We will construct autoantigen-presenting B lymphocytes by transfecting CH12 tumor cells with anti-Sm H and L chains, and will examine peptides bound to their surface class Il MHC molecules. The role of MHC in development of the T-cell receptor repertoire in lpr mice will be examined using class I- and class Il-deficient lpr mice. These studies are expected to elucidate the cellular mechanisms responsible for autoantibody production in this murine model.

拟议的研究将侧重于主要 组织相容性复合物（MHC）在自发性系统性自身免疫中的作用 表达lpr基因的小鼠的疾病。我们发现MHC 等位基因修饰了该小鼠模型中的自身免疫。我们将利用 的许多重组小鼠品系，以定位负责 MHC基因。我们将利用独特的lpr重组小鼠品系， 询问自身抗体产生背后的T-B细胞协作是否 受MHC分子的限制。最近的技术 使得有可能鉴定加工的抗原相关的肽， 与表面MHC分子结合。我们将分离出II类MHC分子， LPR小鼠，并确定与它们相关的肽。这些 这些研究有望为T细胞识别肿瘤的性质提供线索。 自身抗原我们还将确定由蛋白质产生的肽。 通过正常人的抗原呈递细胞和 自体免疫小鼠我们将构建自身抗原呈递B淋巴细胞， 用抗Sm H和L链转染CH 12肿瘤细胞， 检测与其表面II类MHC分子结合的肽。的作用 MHC在lpr小鼠T细胞受体库发育中的作用将 使用I类和II类缺陷型lpr小鼠进行检查。这些研究 有望阐明细胞机制， 自身抗体的产生。