Rat T-cell lines specific to a nonimmunodominant determinant of a retinal protein (IRBP) produce uveoretinitis and pinealitis

Rat lymphocyte lines were established, with specificity toward two synthetic peptides derived from the interphotoreceptor retinoid-binding protein (IRBP), which specifically localizes in the retina and pineal gland. One of the peptides, R4, is immunopathogenic, producing experimental autoimmune uveoretinitis (EAU) and pinealitis (EAP) in immunized rats, while the other peptide, R3, exhibits no detectable immunopathogenicity in rats. The cell lines carry surface markers specific for the helper/inducer subset of T-lymphocytes. When tested by the proliferation assay, the line cells demonstrated major histocompatibility-restricted vigorous responses against the immunizing (homologous) peptide, but failed to recognize the intact IRBP molecule. This finding is in line with other data indicating that peptides R3 and R4 are nonimmunodominant determinants of IRBP for the Lewis rat. Yet, the cell lines specific for R4 were highly immunopathogenic, producing EAU and EAP in naive rats at numbers as low as 0.25 x 10(6), with histopathological changes similar to those induced by active immunization with this peptide. The immunological capacity of the cell lines was further demonstrated by the finding that spleen cells from recipient rats of these lines responded well against the homologous peptides. The uniqueness of this system, in which lymphocytes specific toward a nondominant determinant are immunopathogenic, is underscored and the possible mechanisms of disease induction are discussed.