HETEROLOGOUS EPITOPES OF IRBP PROTECT AGAINST AUTOIMMUNE UVEITIS INDUCED BY THE AUTOLOGOUS EPITOPE

Peptide 161-180 of human interphotoreceptor retinoid-binding protein ( IRBP) contains a major uveitogenic epitope for mice of the H-2(r) hapl otype. The human and bovine homologs differ from the autologous murine homolog by three and four amino acid residues, respectively. We compa re the immunogenicity and pathogenicity of the three homologs, and inv estigate their ability to induce oral tolerance to experimental autoim mune uveoretinitis (EAU) induced by the autologous peptide. All three 161-180 homologs were pathogenic, with a hierarchy: human > murine > b ovine. All crossreacted with each other and with IRBP. Feeding any of the three homologs (6 x 200 mu g over 2 weeks) lowered antigen-specifi c responses and protected from EAU induced by the autologous homolog, and reduced EAU induced with whole IRBP. Peptide-fed mice had a reduce d frequency of peptide-reactive T cells, suggesting a mechanism involv ing anergy and/or deletion. The results indicate that non-identical, b ut crossreactive, heterologous epitopes can protect against EAU induce d by the corresponding autologous epitope, and even by the whole multi -epitope protein. These findings may impact on clinical trials in whic h uveitis patients are undergoing oral immunotherapy with bovine retin al antigens. Published by Elsevier Science B.V.