MOLECULAR BIOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEITIS

点击翻译按钮获取中文摘要

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.