Retinal s-antigen (SAg) and interphotoreceptor retinol-binding protein (IRBP) induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are good models for studying the mechanisms involved in autoimmune diseases. Many immunogenetically active epitopes have been identified in these proteins but immunodominance of one or more epitopes in vivo, has not yet been established. In this paper we present and discuss some experiments that led to the discovery of a dominant“tolerogenic”epitope in SAg. We also demonstrate the presence of cross reactive epitopes in the two potent retinal antigens, SAg and IRBP and finally introduce early data on a unique anti S2.4.C5 idiotypic (Id) monoclonal antibody (MAb) which appears to be a site non associated antibody that binds not only to S2.4.C5 but also to SAg.