Identification of T cell recognition sites in S-antigen: dissociation of proliferative and pathogenic sites.
Experimental autoimmune uveoretinitis (EAU) is a predominantly CD4+ T cell-mediated autoimmune inflammatory disease of the retina and uveal tract of the eye and the pineal gland. S-antigen, a protein found in retinal photoreceptor cells and pinealocytes, is a potent agent for the induction of EAU in susceptible species and strains. In order to identify the T cell recognition sites of S-antigen responsible for its uveitogenicity and proliferative responses, cyanogen bromide (CB) fragments as well as synthetic peptides were used to test the proliferative responses of two uveitogenic T cell lines, R9 and R17, prepared against native bovine and human S-antigen, respectively. Two nonoverlapping synthetic peptides which are known to actively induce EAU, amino acid residues 286-297 and 303-314 of the bovine sequence, were unable to induce proliferative responses in either S-antigen-specific T cell line. 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 strong proliferative responses from T cell lines raised to bovine and human S-antigen. Repeated in vitro selection of the R9 T cell line with a synthetic peptide containing one of these proliferative sites, residues 317-328, gave rise to a transiently uveitogenic T cell line. Several species-specific T cell epitopes were identified, but none of these were found to be involved in a uveitogenic response. Our results indicate that spatially separated and distinct T cell epitopes are present in S-antigen which are responsible for the active induction of EAU, lymphocyte proliferation, and the ability to adoptively transfer EAU.
Gregerson
D S
DS
Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Fling
S P
SP
Obritsch
W F
WF
Merryman
C F
CF
Donoso
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D019393:Arrestin; D001327:Autoimmune Diseases / Q000276:immunology*; D002417:Cattle; D005136:Eye Proteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*
D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell