MOLECULAR BIOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEITIS

之前已经确定了人、小鼠、大鼠、 和牛视网膜S抗原和大鼠松果体S抗原，我们还 确定了葡萄膜的免疫致病部位和4个致病部位 S-抗原。其中两个免疫原性序列在 这些物种。 国家生物医学研究基金会数据库中的许多蛋白质都有 与葡萄膜炎致病部位相似的序列。我们化学合成了 多种多肽及部分多肽诱导实验性自身免疫性葡萄膜炎 (EAU)和实验性自身免疫性松果体炎(EAP)。那些 从酵母菌(Saccharmyces)合成的包括合成肽 酿酒酵母)组蛋白H3，大肠杆菌假设蛋白，马铃薯 蛋白酶抑制物，肝炎病毒蛋白，Moloney小鼠肉瘤病毒 蛋白和Moloney鼠白血病病毒蛋白。另外，我们发现， 天然酵母组蛋白H3也能诱导EAU。 口服酵母组蛋白的动物 抑制酵母组蛋白H3诱导的EAU和EAP 或S抗原肽。因此，具有分子的多肽 模仿交叉诱导了这种耐受性。这些发现为以下研究提供了依据 了解人类眼睛的自身免疫性炎症性疾病。 阐明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 以及六种不同的被杀细菌中的一种，无论有没有 不完全弗氏佐剂(IFA)。注射IFA的大鼠出现了 EAU，但大多数注射不含IFA的大鼠并未发展为EAU。要评估 活体微生物感染的影响，我们给大鼠注射了几次 用低剂量的表达S抗原的活大肠杆菌和 有交叉反应抗原的贝克氏酵母。给大鼠注射 要么是活的大肠杆菌，要么是活的酵母产生了EAU。我们的结论是 由具有交叉反应抗原的微生物感染可以打破 自身抗原免疫耐受与炎症性自身免疫 疾病。

Having previously determined the amino acid sequences of human, mouse, rat, and bovine retinal S-antigen and rat pineal gland S-antigen, we also determined the immunogenic sites and four uveitopathogenic sites of S-antigen. Two of the immunogenic sequences were highly conserved among these species. Many proteins in the National Biomedical Research Foundation data base have a similar sequence with a uveitopathogenic site. We chemically synthesized many peptides and some of them induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats. Those synthesized include synthetic peptides from yeast (Saccharomyces cerevisiae) histone H3, Escherichia coli hypothetical protein, potato proteinase inhibitor, hepatitis virus protein, Moloney murine sarcoma virus protein, and Moloney murine leukemia virus protein. In addition, we found that native yeast histone H3 was also capable of inducing EAU. The animals which were administrated yeast histone by the oral route suppressed the induction of EAU and EAP induced by either yeast histone H3 peptide or a S-antigen peptide. Thus, the peptides which have molecular mimicry cross-induced the tolerance. These findings provide a basis for understanding autoimmune inflammatory diseases of the eye in humans. To elucidate the role in autoimmunity of infectious microorganisms that have cross-reactive antigens, we injected Lewis rats with peptide M together with one of six different killed bacteria, either with or without incomplete Freund's adjuvant (IFA). The rats injected with IFA developed EAU, but most rats injected without IFA did not develop EAU. To assess the impact of infection by live microorganisms, we injected rats several times with low doses of both live Escherichia coli that express S-antigen and baker's yeast that has a cross-reactive antigen. The rats injected with either live Escherichia coli or live yeast developed EAU. We conclude that infection by microorganisms that have cross-reactive antigens can break immune tolerance to self-antigens and induce inflammatory autoimmune diseases.