Functional Dissociation of T Cell Sites; Immunogenic, Antigenic and Pathogenic Sites

Abstract

Experimental autoimmune uveoretinitis (EAU) is a CD4⁺ T-cell mediated autoimmune disease induced by S-antigen, a retinal photoreceptor cell protein. In order to identify T cell recognition sites responsible for pathogenicity, cyanogen bromide fragments and synthetic peptides were used to test uveitogenic T cell lines prepared against native S-antigen. Two non-overlapping synthetic peptides known to actively induce EAU did not induce proliferative responses in these T cell lines. In contrast, an adjacent synthetic peptide which was unable to actively induce EAU elicited strong proliferative responses from the T cell lines and gave rise to a uveitogenic line. Our results indicate that spatially 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.

This work was supported by NIH grants EY-05417 (D.S.G.), EY-05095 (L.A.D.), Research to Prevent Blindness, the Crippled Children’s Vitreo-Retinal Research Foundation (L.A.D.), and the Pennsylvania Lions Sight Conservation and Eye Research Foundation (L.A.D.). D.S.G. is a Research to Prevent Blindness Senior Scientific Investigator.