IMMUNE MECHANISMS OF OCULAR INFLAMMATORY DISEASE

候选人的近期目标是发展科学专长 在分子免疫学和眼生物化学中， 致病性自身抗原的定义。这将导致长期的 一个独立的研究项目的目标是对眼的发病机制， 炎症性疾病。候选人有很强的临床背景 眼科学，对眼部炎症表现出兴趣。过去 研究生院在基础研究方面的成功证明了她的科学 能力.然而，从研究生院到重新入学的滞后时间 进入基础研究需要一段时间的指导科学再培训。 加州大学洛杉矶分校将提供一个优秀的科学环境， 候选人发展目前的分子生物学专业知识， 免疫学该项目的健康相关性在于， 试图定义驱动某些内源性人免疫球蛋白的候选抗原， 眼睛的炎症性疾病，这可以作为基础， 新的诊断测试和治疗干预。 虽然许多免疫介导的炎症性疾病被认为是导致 从活化的CD 4 T细胞、B细胞活化和克隆扩增， 预计会同时发生。这些选择的B细胞具有相同的 病原性T细胞的抗原特异性及其抗体 提供了一个重要的工具，以表征驱动 免疫反应这项提案的主题是使用新技术 iii抗体噬菌体展示克隆以分离标记抗体， 一种常见的特异性葡萄膜炎的候选抗原 溃疡性结肠炎（UC）第一个目标是确定一个 UC中的独特标记抗体pANCA与炎症相关 葡萄膜炎这将通过ELISA和免疫荧光筛查进行检测 pANCA的不同UC形式的人血清。的相关性 还将确定疾病活动性和自身抗体水平。的 第二个目的是鉴定与人5-3反应的葡萄膜抗原， pANCA抗原的重组单克隆抗体。如果这些抗原 被鉴定，将通过蛋白质生物化学对其进行表征，或 如果需要，通过分子克隆。抗原的疾病关联 将通过表征B和T细胞对 抗原的第三个目标是建立一个综合性的葡萄膜库 与UC抗体应答反应的抗原。生化和 将对这些抗原进行免疫学表征 根据上述目标的实验模型。

The immediate goal of the candidate is to develop scientific expertise in molecular immunology and ocular biochemistry as applied to the definition of pathogenic autoantigens. This will lead to the long-term goal of an independent research program on the pathogenesis of ocular inflammatory diseases. The candidate has a strong background in clinical ophthalmology with a demonstrated interest in ocular inflammation. Past graduate school success in basic research is evidence of her scientific abilities. However, the lag time between graduate school and re-entry into basic research demands a period of mentored scientific retraining. UCLA will provide an outstanding scientific environment that will allow the candidate to develop current expertise in molecular biology and immunology. The health-relatedness of the project is that it specifically attempts to define candidate antigens that drive certain endogenous human inflammatory diseases of the eye, which can be used as the basis for novel diagnostic tests and therapeutic interventions. Although many immune-mediated inflammatory diseases are thought to result from activated CD4 T cells, B cell activation and clonal expansion is expected to occur in tandem. These selected B cells have the same antigenic specificity of the pathogenic T cell, and their antibodies offer an important tool to characterize the target antigen driving the immune response. The subject of this proposal is to use new techniques iii antibody phage display cloning to isolate marker antibodies and candidate antigens for a distinctive type of uveitis that commonly occurs with ulcerative colitis (UC). The first aim is to determine whether a unique marker antibody in UC, pANCA, is associated with inflammatory uveitis. This will be tested by ELISA and immunofluorescence screening of human sera for the distinct UC form of pANCA. The correlation between disease activity and level of autoantibody will also be determined. The second aim is to identify uveal antigens that react with 5-3, a human recombinant monoclonal antibody to the pANCA antigen. If such antigens are identified, they will be characterized by protein biochemistry, or if necessary, by molecular cloning. Disease association of the antigen will be tested by characterizing the B and T cell responses to the antigen. The third aim is to develop a comprehensive library of uveal antigens reactive with the UC antibody response. Biochemical and immunologic characterization of these antigens will be performed following the experimental model of the preceding aim.