Immune responses to peptides derived from the retinal protein IRBP: Immunopathogenic determinants are not necessarily immunodominant

Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific to the retina and pineal gland, induces in immunized rats inflammatory changes in these organs (EAU and EAP, respectively). We report here on the immunological activities in Lewis rats of 10 IRBP-derived peptides. Only one of these peptides (R3) was found to induce high levels of antibodies in immunized rats, as detected by ELISA. On the other hand, the majority of the tested peptides stimulated substantial cellular immune responses, measured by the lymphocyte proliferation assay. None of the tested peptides were recognized, however, by antibodies or lymphocytes from rats immunized with the whole IRBP molecule, thus indicating that these synthetic peptides are nonimunodominant in the Lewis rat. Two of these peptides, R4 and R9 (which contains R4), were previously found to be immunopathogenic, producing EAU and EAP in immunized Lewis rats. The immune responses to peptide R4 were further examined and the data show that it induces measurable lymphocyte responses only when injected at remarkably high doses (≥67 μg/rat). Yet, peptide R4 was highly antigenic when tested for stimulation of specifically sensitized lymphocytes in culture. Furthermore, lymphocytes sensitized against R4 exhibited high capacity to adoptively transfer EAU and EAP to naive recipients. The finding of immunopathogenic but nonimmunodominant peptides is discussed.