T-CELL CONTROL OF AUTOREACTIVITY IN SLE

拟议的研究将集中在专业人员的作用上 自发性全身自身免疫中的组织相容性复合体 表达LPR基因的小鼠的疾病。我们发现MHC 在这个小鼠模型中，等位基因改变了自身免疫。我们会利用这个优势 在许多重组小鼠品系中定位责任 MHC基因。我们将利用独特的LPR重组小鼠品系来 问：T-B细胞的协作是否是自身抗体产生的基础 在这个模型中受到MHC分子的限制。最新技术 使鉴定与加工抗原相关的多肽成为可能 表面的MHC分子。我们将分离出第二类MHC分子 并确定与它们相关的多肽。这些 研究有望为T细胞识别的本质提供线索。 自身抗原。我们还将确定由 正常人和正常人的抗原提呈细胞对已知自身抗原的处理 自身免疫的小鼠。我们将通过以下方式构建自身抗原呈递的B淋巴细胞 用抗Sm H和L链转染CH12肿瘤细胞 检查与其表面类Il MHC分子结合的多肽。角色 MHC在LPR小鼠T细胞受体谱系发展中的作用 使用I类和Il类缺陷的LPR小鼠进行检测。这些研究 有望阐明导致这些疾病的细胞机制 在这个小鼠模型中产生自身抗体。

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.