S-ANTIGEN--STRUCTURE/FUNCTION RELATIONSHIPS IN UVEITIS

1973年，Kalsow和Wacker定位了负责免疫缺陷病毒的抗原。 在动物中诱导实验性自身免疫性葡萄膜炎（EAU）， 包围着视网膜的感光细胞。 随后瓦克和 Donoso（1975）分离、纯化并表征了这种高度 来自牛视网膜的葡萄膜病原蛋白，命名为S抗原。 更 最近，S抗原与某些形式的人类葡萄膜炎有关 如鸟枪弹样视网膜脉络膜病变和交感性眼炎。 最近 Jakobiec和同事（1983年）在一项优雅的研究中， 交感性眼炎是一种局限性T细胞迟发性超敏反应 异常 尽管有许多关于病理和 EAU的免疫学特征，几乎没有关于 抗原位点的性质和结构/功能关系 这种重要的蛋白质。 我们建议研究牛和人的结构/功能关系 视网膜S抗原 生化研究将包括产生轻微的 完整天然S抗原的修饰。 这些修改将 通过使用与特定氨基酸基团反应的试剂产生 在温和的条件下，可以定量测量。 的 这些修饰对S抗原抗原性的影响将是 通过ELISA测定和使用EAU动物模型测定。 的 将使用标准品测定S抗原的氨基酸序列 技术和自动氨基酸测序仪。 免疫学研究 将包括杂交瘤分泌的单克隆抗体的生产 将S抗原免疫小鼠的脾细胞与小鼠融合， 骨髓瘤细胞系SP 2/0.Ag 14。 这些抗体将用于 检查牛和人S抗原之间抗原表位的差异 这些研究将有助于更好地了解生物化学， 免疫学的S-抗原，并可以确定网站的免疫相互作用的EAU。

In 1973 Kalsow and Wacker localized the antigen responsible for the induction of experimental autoimmune uveitis (EAU) in animals to completely surround the photoreceptor cells of the retina. Subsequently Wacker and Donoso (1975) isolated, purified and characterized this highly uveitopathogenic protein designated S-antigen from bovine retina. More recently S-antigen has been implicated in certain forms of human uveitis such as birdshot retinochoroidopathy and sympathetic ophthalmia. Recently Jakobiec and associates (1983) in an elegant study characterized sympathetic ophthalmia as a localized T cell delayed hypersensitivity abnormality. Despite numerous reports concerning the pathologic and immunologic feature of EAU, almost no information is available regarding the nature of the antigenic sites and structural/functional relationships of this important protein. We propose to study structure/function relationships of bovine and human retinal S-antigen. Biochemical studies will consist of producing slight modification of the intact native S-antigen. These modifications will be produced by using reagents which react with specific amino acid groups under mild conditions and which can be measured quantitatively. The effects of these modifications on the antigenicity of S-antigen will be determined by the ELISA assay and by using the animal model of EAU. The amino acid sequence of S-antigen will be determined using standard techniques and the automated amino acid sequenator. Immunologic studies will consist of the production of hybridoma secreted monoclonal antibodies by fusing spleen cells form mice immunized with S-antigen with the mouse myeloma cell line (SP 2/0.Ag 14). These antibodies will be utilized to examine differences in antigenic epitopes between bovine and human S-antigen These studies will lead to a better understanding of the biochemistry and immunology of S-antigen and may identify sites of immune interaction in EAU.