MOLECULAR BIOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEITIS

我们之前测定了人、小鼠、 大鼠，牛视网膜S抗原和大鼠松果体S抗原。 S抗原的免疫原部位和四个葡萄膜病变部位 已经下定决心。其中两个免疫原性序列是高度 在这些物种中保存下来。 国家生物医学研究基金会数据库中的许多蛋白质 具有与葡萄膜炎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 自身免疫性葡萄膜炎(EAU)和实验性自身免疫性松果体炎(EAP) 在刘易斯大鼠身上。这些多肽包括从酵母中合成的多肽 (酿酒酵母)组蛋白H3，大肠杆菌假说 蛋白质，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小鼠白血病病毒 蛋白。此外，天然酵母组蛋白H3能够诱导 真的。 口服酵母组蛋白的动物受到抑制 酵母组蛋白H3肽对EAU和EAP的诱导作用 也不是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。这些发现提供了依据 用于人类眼睛的自身免疫性炎症性疾病。 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大鼠注射了多肽 我和六种不同的被杀死的细菌中的一种一起，要么是 不含不完全弗氏佐剂(IFA)。注射IFA的大鼠 发生EAU，但大多数注射不含IFA的大鼠没有发生EAU。 为了评估活体微生物感染的影响，我们注射了 用小剂量活大肠杆菌多次免疫大鼠，表达S- 抗原和面包酵母与交叉反应抗原。那些老鼠 注射活的大肠杆菌或活的酵母菌会产生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。

We previously determined the 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 also were determined. Two of the immunogenic sequences were highly conserved among these species. Many proteins in the National Biomedical Research Foundation data base have sequences 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. The peptides 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, native yeast histone H3 was capable of inducing EAU. The animals administered yeast histone by the oral route suppressed the induction of EAU and EAP by either the yeast histone H3 peptide or an S-antigen peptide. Thus, the peptides that have molecular mimicry cross-induced the tolerance. These findings provide a basis for autoimmune inflammatory diseases of the eye in humans. 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, 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 the rats several times with low doses of live E. coli expressing S- antigen and baker's yeast with a cross-reactive antigen. The rats injected with either live E. 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.