S-ANTIGEN--STRUCTURE/FUNCTION RELATIONSHIPS IN UVEITIS

点击翻译按钮获取中文摘要

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.