Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals. We report here on the identification of an immunodominant determinant of bovine IRBP that is highly immunogenic and immunopathogenic in the Lewis rat. The peptide, which comprises the sequence 1169-1191 of bovine IRBP, was shown to be immunodominant by its capacity to stimulate lymphocytes sensitized against whole IRBP. A comparison was made between peptide 1169-1191 and another peptide, 1158-1180, which is nondominant but is immunogenic and immunopathogenic in the Lewis rat. Peptide 1169-1191 was found to be superior in its immunological capacities; the minimal dose of 1169-1191 needed to induce cellular immune response or disease in Lewis rats (0.02-0.1 nmol/rat) is congruent to 1,000 times smaller than that of 1158-1180. In addition, unlike the ocular disease induced by 1158-1180, the disease produced by 1169-1191 resembled that induced by whole IRBP in its kinetics and histopathological features. The immunological activity of 1169-1191 in the Lewis rat was localized to the 10 residues at the COOH terminus; no such activity was exhibited by the truncated peptide 1169-1188, which comprises the 20 residues at the NH2 terminus of the full peptide. The usefulness of this unique experimental system in analyzing the role of immunodominance in peptide immunogenicity and immunopathogenicity is underscored.
Lens-induced uveitis can be elicited in experimental animals by immunization with lens antigens, followed by puncture of the lens capsule. The animal disease, that serves as a model for the human disease (also known as phacoanaphylactic endophthalmitis), has been shown to be mediated by antibodies against the lens antigens. Here the authors report on a new disease model for lens-induced uveitis which is cell-mediated. This experimental disease is induced in transgenic (Tg) mice that express hen egg lysozyme (HEL) in their lens. Eyes of these mice show disrupted lens, but no inflammation. On the other hand, severe inflammation develops in eyes of these Tg mice following intraperitoneal injection of lymphocytes from syngeneic wildtype donors sensitized against HEL. Furthermore, the recipient mice exhibit intense cellular immunity but no antibodies against HEL.
SUMMARY The retinal S-antigen (S-Ag) has been shown to induce uveitis effectively in subhuman primates, and lymphocytes from patients with certain uveitic conditions show cell-mediated responses to this antigen. Rhodopsin kinase (RK), an enzyme probably unique to the mammalian eye, is reported here to resemble the retinal S-Ag in its capacity to induce uveitis in experimental animals. A histological comparison of rat eyes taken 2 and 3 weeks after immunisation with either RK or S-Ag reveals essentially identical pathological alterations. Ocular inflammation is seen in both the anterior and posterior portion of the globe. Areas of focal degeneration of the photoreceptor layer, from which both the S-Ag and RK are extracted, could be seen in both RK and S-Ag immunised animals. Cells from draining lymph nodes of both groups responded by increased thymidine incorporation when cultured in the presence of either RK or S-Ag. In addition antibodies directed against the S-Ag were detected in both groups. These findings, in addition to the biochemical similarities of these preparations, reported elsewhere, would strongly suggest that RK 'and S-Ag are one and the same. The identification of potentially uveitogenic ocular antigens could help to reclassify uveitic entities that at present have clinically similar courses.
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