Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats.
S-Antigen (S-Ag) is a well characterized 45,000 m.w. photoreceptor cell protein. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis, a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and of the pineal gland. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag, several viral proteins and one additional nonviral protein. An experimental autoimmune uveitis and pinealitis was induced in Lewis rats with these different synthetic peptides, corresponding to the amino sequence of hepatitis B virus DNA polymerase, gag-pol polyprotein of Baboon endogenous virus and gag-pol polyprotein of AKV murine leukemia virus and potato proteinase inhibitor IIa, which contain three or more consecutive amino acids identical to peptide M in S-Ag. Lymph node cells from rats immunized with either peptide M or the different synthetic peptides showed a significant degree of cross-reaction. Mononuclear cells from monkeys (Macaca fascicularis) immunized with peptide M also showed significant proliferation when incubated with either peptide M or synthetic peptides as measured by in vitro lymphocyte mitogenesis assay using [3H]TdR. Based on our findings we conclude that a viral infection may sensitize the mononuclear cells that can cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoantigenic event can take place in the absence of the infectious virus that initiated the immune response.
Molecular Biology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
V K
VK
Singh
H K
HK
Kalra
K
K
Yamaki
T
T
Abe
L A
LA
Donoso
T
T
Shinohara
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D019393:Arrestin; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D003429:Cross Reactions; D004259:DNA-Directed DNA Polymerase / Q000276:immunology*; D000939:Epitopes; D005136:Eye Proteins / Q000276:immunology*; D015685:Fusion Proteins, gag-pol / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D010870:Pineal Gland / Q000276:immunology; D011480:Protease Inhibitors / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D000939:Epitopes; D005136:Eye Proteins; D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D009842:Oligopeptides; D011480:Protease Inhibitors; D004259:DNA-Directed DNA Polymerase