Donoso L A, Merryman C F, Sery T W, Shinohara T, Dietzschold B, Smith A, Kalsow C M
Research Department, Wills Eye Hospital, Philadelphia, PA.
Curr Eye Res. 1987 Sep;6(9):1151-9. doi: 10.3109/02713688709034888.
S-antigen (48K protein) is a photoreceptor cell protein highly pathogenic for the induction of experimental autoimmune uveitis (EAU) and intimately involved in the visual process. EAU is characterized, in part, as a T-cell mediated autoimmune disease which results in a severe inflammation of the uveal tract, and pineal gland. In order to determine specific sites in S-antigen responsible for its pathogenicity we synthesized twenty-three peptides, corresponding to the entire 404 amino acid sequence, and tested each peptide for its ability to induce EAU in Lewis rats. One peptide, peptide M (18 amino acids in length), was found to be highly pathogenic and consistently induced an EAU that was identical to the disease caused by native S-antigen. Clinically, the disease that developed in the eye was characterized by iris and pericorneal hyperemia, followed by inflammatory exudates in the anterior and vitreous chambers. Histopathologically a severe inflammatory response was observed which resulted in the complete destruction of the photoreceptor cell layer of the retina. In order to more fully characterize this pathogenic site, 14 additional smaller peptides (eight to eighteen amino acids in length) corresponding to the left and right portions of peptide M were synthesized. Of these peptides, peptide M16L, M15L, and M12L induced EAU, further localizing this pathogenic site to a small well-characterized region of S-antigen consisting of twelve amino acids. In addition, animals with ocular inflammatory disease had an associated pinealitis characterized by a lymphocytic infiltration of the subcapsular and central area of the pineal gland. The significance of these findings and the relationship of S-antigen in the pathogenesis of EAU and other autoimmune diseases is discussed.
S抗原（48K蛋白）是一种光感受器细胞蛋白，对诱导实验性自身免疫性葡萄膜炎（EAU）具有高度致病性，并且与视觉过程密切相关。EAU部分特征为一种T细胞介导的自身免疫性疾病，可导致葡萄膜和松果体的严重炎症。为了确定S抗原中负责其致病性的特定位点，我们合成了二十三种与整个404个氨基酸序列相对应的肽，并测试了每种肽在Lewis大鼠中诱导EAU的能力。发现一种肽，即肽M（长度为18个氨基酸）具有高度致病性，并始终诱导出与天然S抗原引起的疾病相同的EAU。临床上，眼部出现的疾病特征为虹膜和角膜周围充血，随后在前房和玻璃体腔出现炎性渗出物。组织病理学观察到严重的炎症反应，导致视网膜光感受器细胞层完全破坏。为了更全面地表征这个致病位点，合成了另外14种较小的肽（长度为8至18个氨基酸），它们对应于肽M的左右部分。在这些肽中，肽M16L、M15L和M12L诱导了EAU，进一步将这个致病位点定位到S抗原的一个由十二个氨基酸组成的小的、特征明确的区域。此外，患有眼部炎症性疾病的动物伴有松果体炎，其特征为松果体囊下和中心区域的淋巴细胞浸润。讨论了这些发现的意义以及S抗原在EAU和其他自身免疫性疾病发病机制中的关系。
