IMMUNOCHEMICAL CHARACTERIZATION OF RETINAL S-ANTIGEN

免疫学过程的研究，特别是自身免疫的基础 眼内炎性疾病提示存在几种 视网膜、视网膜色素上皮中的免疫致病抗原， 脉络膜和视神经。到目前为止，这些抗原中只有一个是 足够纯净并被确凿地证明是葡萄膜生成的； 视网膜S抗原。对S抗原结构的定量研究较少 已有报道，其可能的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 免疫化学方法，并确定其一级结构。对ITS的了解 序列和抗原决定簇可能导致开发和使用 具有治疗作用的触发肽或类似物。因为S的抗原是这样的 其他免疫致病眼部抗原的候选者具有很强的效力 是适当的可疑和特殊措施，以确保他们的活动 不是因为被S污染了-抗原都是必需的。一个后果是 S抗原易分离、易溶的研究 尽管有大量的潜在抗原，但其他潜在的抗原并没有得到大力追查 间接证据。对于膜结合来说尤其如此 更难研究的蛋白质。最近的证据来自我们的 LAB建议对蛋白质膜结合部分的检查 从棒的外部部分是早就应该的，因为它看起来是一个 异常丰富的S以外的抗原蛋白来源-抗原和 视紫红质，另一种假定的葡萄膜生成抗原。我们建议将杆分离出来 并从中提纯出另外两种蛋白质p35和p27。 因为我们有证据表明p35也被血清抗体识别 一些葡萄膜炎患者，将这些分离出来将是最有趣的 足够数量的蛋白质来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的抗原是视紫红质激酶， 那么在这份提案中要收集的结构性信息也将 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.