MOLECULAR BIOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEITIS

我们先前已经确定了人、小鼠、大鼠和小鼠的氨基酸序列， 牛视网膜S抗原和大鼠松果体S抗原。免疫原性位点 并确定了S抗原的四个葡萄膜致病位点。两 免疫原性序列在这些物种中高度保守。 有许多蛋白质具有类似的序列， 国家生物医学研究基金会数据中的葡萄膜致病位点 基地我们化学合成了许多肽，其中一些诱导了 实验性自身免疫性葡萄膜炎（EAU）和实验性自身免疫性葡萄膜炎 刘易斯大鼠中的松果体素（EAP），包括来自酵母的合成肽 （酿酒酵母）组蛋白H3，假设大肠杆菌 蛋白质，马铃薯蛋白酶抑制剂，肝炎病毒蛋白，莫洛尼 鼠肉瘤病毒蛋白和莫洛尼鼠白血病病毒蛋白。在 此外，天然酵母组蛋白H3也能诱导EAU。 有趣的是，口服酵母组蛋白的动物 抑制EAU和EAP诱导的酵母组蛋白H3肽或 S-抗原肽。因此，具有分子模拟的肽 交叉诱导耐受性。这些发现为自身免疫性 人类眼睛的炎症性疾病。

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. There are many proteins which have a similar sequence with a uveitopathogenic site in the National Biomedical Research Foundation data base. We chemically synthesized many peptides, some of which induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats, including 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 also capable of inducing EAU. Interestingly, the animals that were administered the yeast histone orally suppressed the EAU and EAP induction by either yeast histone H3 peptide or a 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.