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(SAg)和大鼠松果体SAg。免疫原性 还确定了SAG的发病部位和4个葡萄膜病变部位；2 免疫原性序列在物种间高度保守。许多 国家生物医学研究基金会数据库中的蛋白质具有 与葡萄膜致病部位相似的序列。我们在化学上 合成了许多多肽，其中一些诱导了实验性的自身免疫 Lewis大鼠葡萄膜炎(EAU)和实验性自身免疫性松果体炎(EAP)。 此外，我们还发现天然酵母组蛋白H3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， 连同六种不同的杀菌之一，无论有没有 不完全弗氏佐剂(IFA)。注射IFA的大鼠出现了 真的。为了评估活体微生物感染的影响，我们 低剂量注射表达SAG和BAKER‘s的活大肠杆菌 酵母与一种具有交叉反应的抗原多次进入大鼠体内。这个 注射活的大肠杆菌或活的酵母的老鼠出现了EAU。我们 结论是由具有交叉反应的微生物感染 抗原可以打破对自身抗原的免疫耐受，并诱导 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 在这个问题上，我们进行了类似的实验：三组，四只大鼠 三次注射晶状体匀浆、β-晶状体蛋白或 β-晶状体蛋白(B-A1)与完全弗氏佐剂(CFA)乳化。 所有动物在5周内均出现晶状体上皮细胞严重损伤。 从第一次注射之日起。给大鼠注射一种合成的 鼠伤寒沙门氏菌蛋白多肽，含5个氨基酸 与大鼠β-晶状体蛋白(β-B2)相同的酸性残基也被诱导 类似的损坏。由具有与该病毒同源抗原的微生物感染 晶状体抗原可以诱导高水平的自身抗体，从而激发晶状体 上皮细胞受损。因此，晶状体上皮细胞中的自身免疫损伤 可能是白内障形成初期的一种病因学。我们的未来 研究将更多地集中在晶状体白内障发生中的自身免疫。

We had previously determined amino acid sequences of human, mouse, rat, and bovine retinal S-antigen (SAg) and rat pineal gland SAg. Immunogenic sites and four uveitopathogenic sites of SAg also were determined; two immunogenic sequences were highly conserved among the species. Many proteins in the National Biomedical Research Foundation database have a sequence similar to that of a uveitopathogenic site. We chemically synthesized many peptides, some of which induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats. In addition, we found native yeast histone H3 capable of inducing EAU. To understand the role in autoimmunity of infectious microorganisms which have cross-reactive antigens, we injected Lewis rats with peptide M, together with one of six different killed bacteria, with or without incomplete Freund's adjuvant (IFA). The rats injected with IFA developed EAU. To assess the impact of infection by live microorganisms, we injected low doses of live Escherichia coli expressing SAg and baker's yeast with a cross-reactive antigen into the rats several times. The rats injected with either live E. coli or live yeast developed EAU. We conclude that infection by microorganisms which 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 conducted similar experiments: Three groups of four rats were injected three times with lens homogenate, beta-crystallins, or a beta-crystallin (B-A1) emulsified with complete Freund's adjuvant (CFA). All the animals developed severe damage in lens epithelial cells 5 weeks from the date of the first injection. The rats injected with a synthetic peptide derived from Salmonella typhimurium protein, which has five amino acid residues identical to rat beta-crystallin (beta-B2), also induced similar damage. Infection by microbes having antigens homologous to the lens antigens can induce high levels of autoantibodies that provoke lens epithelial cell damage. Thus, autoimmune insult in lens epithelial cells may be an etiology of an initial stage of cataractogenesis. Our future research will focus more on autoimmunity in lens cataractogenesis.