Human S-antigen: characterization of uveitopathogenic sites.
Human S-antigen (HSA) is a 50,000 molecular weight photoreceptor cell protein capable of inducing an experimental autoimmune uveitis (EAU) in susceptible animal strains. In order to determine specific sites responsible for its uveitopathogenicity, we synthesized 39 overlapping peptides corresponding to its entire 404 amino acid sequence and tested each peptide for its ability to induce an EAU in Lewis rats. Two synthetic peptides designated peptide HSA 319 (amino acid positions 286 to 305) and peptide HSA 320 (amino acid positions 306 to 325) were uveitopathogenic when used at 50 and 100 micrograms immunizing doses. Smaller peptides corresponding to the amino, mid, and carboxy terminal portions of each peptide further refined each uveitopathogenic site to 12 amino acids. A computerized analysis of the amino acid sequence of S-antigen indicates that these uveitopathogenic sites are complex and may be related to a two-fold symmetry in the molecule. Our present and previous studies provide a basis for the uveitopathogenicity of human and bovine S-antigen in the pathogenesis of EAU as well as the pathogenesis of certain forms of uveitis in humans.
Donoso
L A
LA
Wills Eye Hospital, Biochemistry and Molecular Biology Department, Thomas Jefferson University, Philadelphia, PA.
Yamaki
K
K
Merryman
C F
CF
Shinohara
T
T
Yue
S
S
Sery
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D019393:Arrestin; D001324:Autoantigens / Q000032:analysis; D000939:Epitopes / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010449:Peptide Mapping; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000209:etiology* / Q000473:pathology
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D000939:Epitopes; D005136:Eye Proteins; D010446:Peptide Fragments