MOLECULAR BIOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEITIS

我们之前已经测定了人、小鼠、大鼠、 牛视网膜S抗原和大鼠松果体S抗原。免疫原性 还确定了S抗原的部位和4个葡萄膜病变部位。 其中两个免疫原性序列高度保守 物种。 许多与葡萄膜致病部位具有相似序列的蛋白质是 在国家生物医学研究基金会的数据库中。我们在化学上 合成了许多多肽，其中一些诱导了实验 自身免疫性葡萄膜炎和实验性自身免疫性松果体炎 刘易斯老鼠。此外，天然酵母组蛋白H3也能够 诱导EAU。 了解感染性微生物在自身免疫中的作用 有交叉反应的抗原，我们给Lewis大鼠注射了M肽 带有六种不同杀灭细菌中的一种，有或没有未完成 弗洛因德佐剂(IFA)。注射IFA的大鼠出现EAU。至 评估活体微生物、低剂量活体E感染的影响 表达S抗原的大肠埃希菌和具有交叉反应抗原的面包酵母， 给大鼠注射了几次。给大鼠注射L或 E 大肠埃希菌或活酵母产生EAU。我们得出的结论是，通过微型病毒感染 具有交叉反应抗原的生物体可以破坏对 自身抗原，并诱发炎症性自身免疫性疾病。 作为我们之前EAU研究的扩展，我们推测一些 各种类型的白内障可能是由自身免疫性侮辱引起的。去调查 本课题我们也进行了类似的实验。三组，每组四只大鼠 三次注射晶状体匀浆，β-晶体蛋白或β-晶体蛋白- 晶体蛋白(β-A1)与完全弗氏佐剂(CFA)乳化。全 动物在5周后晶状体上皮细胞出现严重损伤。 从第一次注射之日起。给大鼠注射一种合成的 鼠伤寒沙门氏菌五氨基多肽 与大鼠β-晶状体蛋白(β-B2)相同的酸性残基也可诱导SIMIL 损坏。对晶状体有同源抗原的微生物感染 抗原可以诱导高水平的自身抗体，从而造成损害。 到晶状体上皮细胞。因此，晶状体上皮细胞中的自身免疫性损伤 细胞可能是白内障形成初期的一种病因。指令 我们未来研究的重点将是更多地关注晶状体中的自身免疫 白内障的发生。

We have previously determined amino acid sequences of human, mouse, rat, and bovine retinal S-antigen and rat pineal gland S-antigen. Immunogenic sites and four uveitopathogenic sites of S-antigen were also determined. Two of the immunogenic sequences were highly conserved among these species. Many proteins that have a similar sequence with a uveitopathogenic site are in the National Biomedical Research Foundation database. We chemically synthesized many peptides, and some of them induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats. In addition, native yeast histone H3 was also capable of inducing EAU. To understand the role in autoimmunity of infectious micro-organisms that have cross-reactive antigens, we injected Lewis rats with peptide M togethe with one of six different killed bacteria, either with or without incomplet Freund's adjuvant (IFA). The rats injected with IFA developed EAU. To assess the impact of infection by live micro-organisms, low doses of live E coli expressing S-antigen and baker's yeast, with a cross-reactive antigen, were injected several times into the rats. The rats injected with either l e E. coli or live yeast developed EAU. We conclude that infection by micro- organisms that have cross-reactive antigens can break immune tolerance to self-antigens and induce inflammatory autoimmune diseases. As an extension of our previous EAU research, we speculated that some types of cataracts may be induced by autoimmune insults. To investigate this issue we carried out similar experiments. Three groups of four rats were injected three times with lens homogenate, beta-crystallins or a beta- crystallin (beta-A1) emulsified with complete Freund's adjuvant (CFA). All the animals developed severe damage in lens epithelial cells after 5 weeks from the date of the first injection. The rats injected with a synthetic peptide derived from Salmonella typhimurium protein that has five amino acid residues identical to rat beta-crystallin (beta-B2) also induced simil damage. Infection of microbes having homologous antigens to the lens antigens can induce the auto-antibodies at high levels that provoke damage to the lens epithelial cells. Thus, autoimmune insult in the lens epitheli cells may be an etiology of an initial stage of cataractogenesis. Directio of our future research will be to focus more on the autoimmunity in the len cataractogenesis.