A single amino acid substitution in core residues of S-antigen prevents experimental autoimmune uveitis.
We have previously reported that microbial Ags, having a three- to six-amino-acid-sequence homology with a uveitopathogenic epitope (peptide M) of retinal soluble protein (S-Ag), induce experimental autoimmune uveitis (EAU). Another uveitopathogenic epitope (peptide G) of S-Ag also was characterized. In addition, we have characterized the core sequences by truncating peptides G and M from amino acid and carboxyl termini. In this study, we have further defined the core sequences using synthetic octapeptides with a single amino acid substitution. In addition, the analogues of peptides Gm5 or Mm4 are capable of inhibiting the proliferative response of T-lymphocytes from rats immunized with peptides G-8 or M-8, respectively. Co-injection of a pathogenic peptide with nonpathogenic substitution analogues blocked the induction of EAU. These results suggest that specific nonpathogenic analogues with single amino acid substitution derived from pathogenic peptides have potential for prevention and therapy of autoimmune diseases.
Singh
D P
DP
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Kikuchi
T
T
Singh
V K
VK
Shinohara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics*; D019393:Arrestin; D001324:Autoantigens / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D005136:Eye Proteins; D009842:Oligopeptides; D010446:Peptide Fragments