Unique immunological properties of short forms of the interphotoreceptor retinoid-binding protein derived uveitogenic peptide]

Interphotoreceptor retinoid-binding protein (IRBP) induces experimental autoimmune uveoretinitis in a variety of animals. We have previously shown that sequence 1169-1191 of bovine IRBP has strong uveitogenicity and immunogenicity in Lewis rats. In this study, two completely distinct antigenic sites were detected within a short form of this peptide. One site is localized in sequence 1182-1191. The second site localizes within sequence 1183-1191 and becomes detectable only when tryptophan at 1182 is deleted. Lymphocytes sensitized against the first determinant recognized a longer peptide as well as whole IRBP. Lymphocytes sensitized against the second determinant recognized only two peptides 1184-1191 and 1183-1191. No cross reactivity was detected between these two determinants. Amino acid substitution of tryptophan with alanine or glutamic acid at 1182 in peptide 1182-1191 caused complete loss of uveitogenicity and immunogenicity, while substitution with phenylalanine did not change any immunological activities of the original peptide. The unique immunological properties of IRBP-derived peptides were discussed.