Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2(b) haplotype

Purpose. Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated d isease induced by immunization with interphotoreceptor retinoid binding pro tein (IRBP). Major uveitogenic sites have been identified for mice of the H -2(r) and H-2(k) haplotypes but not for the H-2(b) haplotype. The present c ommunication describes the characterization of an epitope contained in resi dues 1 to 20 of human IRBP that induces EAU in H-2(b) mice. Methods. H-2(b) (C57BL/6, 129/J) and H-2(r) (B10.RIII) mice were immunized with peptide 1-20 or with whole (bovine) IRBP. MU (histopathology) and immu nologic responses (delayed-type hypersensitivity [DTH], lymphocyte prolifer ation, and cytokine production) were assessed after 21 days Results. C57BL/6 mice, 129/J and (129/JxC57BL/6)F1 mice, immunized with 200 to 300 mu g of peptide, developed DTH and MU with scores comparable to tho se induced by 100 mu g IRBP. Their lymphocytes proliferated to the peptide and produced interferon-gamma (but not interleukin-4) and transferred EAU t o syngeneic recipients. Lymphocytes of IRBP-immunized mice also responded t o the peptide. Peptide 1-20-immunized B10.RIII mice failed to develop eithe r disease or immunologic responses. Conclusions. Human IRBP peptide 1-20 contains a major epitope for the H-2(b ) haplotype, which is apparently not presented by the H-2(r) haplotype.