IMMUNOCHEMICAL CHARACTERIZATION OF RETINAL S-ANTIGEN

免疫学研究免疫过程，特别是自身免疫， 眼内炎性疾病提示存在几种 视网膜，视网膜色素上皮， 脉络膜和视神经。 到目前为止，这些抗原中只有一种被 经充分纯化并最终证明是致葡萄膜炎的; 视网膜S抗原 对S抗原结构的定量研究很少 已报道，其推定鉴定为视紫红质激酶， 不确定 我们建议继续对S抗原进行表征 免疫化学和确定其一级结构。 了解其 序列和抗原决定簇可以导致开发和使用 半抗原肽或类似物的治疗。 因为S抗原 在其有效性方面，免疫病原性眼抗原的其它候选物 是适当的怀疑和特殊措施，以确保他们的活动， 不是由于S抗原污染。 的结果 S-抗原易于分离和溶解是研究 其他潜在的抗原尽管有丰富的 间接证据 对于膜结合型，尤其如此 这些蛋白质更难研究。 我们最近的证据显示， 实验室表明，对蛋白质的膜结合部分的检查 从棒外段是早就应该，因为它似乎是一个 除S抗原外异常丰富的抗原蛋白来源， 视紫红质，另一种推定的葡萄膜抗原。 我们建议分离杆 外节并从中纯化两种另外的蛋白质p35和p27。 因为我们有证据表明p35也被来自 对于一些葡萄膜炎患者，分离这些 足够数量的蛋白质以测试它们的免疫致病活性 在动物模型中。 如果视觉研究人员证明S抗原是视紫红质激酶， 那么在这个建议中收集的结构信息也将 有助于理解这种酶及其功能。

Studies of the immunological processes, especially autoimmunity, underlying intraocular inflammatory diseases suggest the presence of several immunopathogenic antigens in the retina, retinal pigment epithelium, choroid and optic nerve. Thus far, only one of these antigens has been sufficiently purified and conclusively demonstrated to be uveitogenic; retinal S-antigen. Little quantitative work on the structure of S-antigens has been reported and its putative identification as rhodopsin kinase is uncertain. We propose to continue characterization of S-antigen immunochemically and to determine its primary structure. Knowledge of its sequence and antigenic determinants could lead to the development and use of haptenic peptides or analogues therapeutically. Because S-antigen is so potent in its effect, other candidates for immunopathogenic ocular antigens are properly suspect and exceptional measures to ensure that their activity is not due to contamination with S-antigen are required. A consequence of the ease of isolation and solubility of S-antigen is that investigation of other potential antigens is not being vigorously pursued despite abundant circumstantial evidence. This is especially true of membrane bound proteins which are much more difficult to study. Recent evidence from our lab suggests that examination of the membrane bound fraction of proteins from the rod outer segments is long overdue since it appears to be an unusually rich source of antigenic proteins other than S-antigen and rhodopsin, another putative uveitogenic antigen. We propose to isolate rod outer segments and purify two additional proteins from them, p35 and p27. Since we have evidence that p35 is also recognized by serum antibodies from some uveitis patients, it would be most interesting to isolate these proteins in sufficient quantity to test them for immunopathogenic activity in animal models. If S-antigen is demonstrated by vision researchers to be rhodopsin kinase, then the structural information to be gathered in this proposal will also contribute to the understanding of that enzyme and its function.