A new perspective of S-antigen from immunochemical analysis.
Elucidation of the amino acid sequences of retinal S-antigens from several species has allowed the fine dissection of T cell and antibody epitopes using synthetic peptides. S-antigen, isolated from retinal rod photoreceptor cells, elicits experimental autoimmune uveoretinitis (EAU), a predominantly CD4+ T-cell mediated autoimmune disease of the retina and uveal tract of the eye and pineal gland. Three uveitogenic T cell lines, R9, R17 and R208, prepared against native bovine S-antigen, human S-antigen and cyanogen bromide peptide CB123, respectively, were used to identify the T cell recognition sites responsible for uveitogenic and proliferative responses. T cell epitopes were found to be clustered into 6 regions, some of which were species-specific. The two synthetic peptides known to actively induce EAU, residues 286-297 and 303-314 of bovine S-antigen, were unable to induce significant proliferative responses in any of the three T cell lines. However, both of these sites were adjacent to synthetic peptides, residues 273-292 and 317-328, respectively, which were unable to actively induce EAU, but elicited proliferative responses from the T cell lines. We also report the presence of a new pathogenic site, also associated with an adjacent proliferative site, together in residues 343-362 of bovine S-Ag. Our results indicate that spatially separate and distinct T cell epitopes are present in S-antigen which are responsible for the active induction of EAU, lymphocyte proliferation, and adoptive transfer of EAU.
Department of Ophthalmology, University of Minnesota, Minneapolis.
D S
DS
Gregerson
S P
SP
Fling
W F
WF
Obritsch
C F
CF
Merryman
L A
LA
Donoso
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D019393:Arrestin; D002417:Cattle; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D000939:Epitopes; D005136:Eye Proteins; D010455:Peptides