S-antigen: from gene to autoimmune uveitis.
Retinal S-antigen (S-Ag) is capable of inducing experimental autoimmune uveitis (EAU) in laboratory animals. EAU may serve as an animal model for studying human uveitis. As a first step we have determined the nucleotide sequence of an S-Ag gene and its cDNAs. The amino acid sequences were deduced from the cDNAs of various animals and human. Four uveitopathogenic sites in bovine S-Ag were characterized. One of the sites (peptide M) has sequence homology with non-self proteins from baker's yeast, potato, E. coli, hepatitis B virus, moloney murine leukemia virus, Moloney murine sarcoma virus, AKR murine leukemia virus and baboon endogenous virus. Mononuclear cells from animals immunized with peptide M showed significant proliferation when incubated with synthetic peptides corresponding to the amino acid sequences of the above-mentioned foreign proteins. In addition, all the peptides induced EAU in Lewis rats with a dose of 10-2000 micrograms. Moreover, native histone H3 from baker's yeast histone H3 induced EAU in Lewis rats. Thus, we found several examples of antigenic mimicry between self and non-self proteins. These findings establish a base to study further the mechanism of autoimmune inflammation.
Molecular Biology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
T
T
Shinohara
V K
VK
Singh
M
M
Tsuda
K
K
Yamaki
T
T
Abe
S
S
Suzuki
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics*; D019393:Arrestin; D001324:Autoantigens / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology*; D005136:Eye Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D014605:Uveitis / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D005136:Eye Proteins; D008565:Membrane Proteins