HSP-derived Peptides Inducing Uveitis and IgG and IgA Antibodies

Heat shock protein (HSP) 65 kD-derived peptides, which specifically stimulate T cells from patients with Behçet's disease (BD), are capable of inducing uveitis in rats. Mycobacterial HSP 65 kD and BD-specific peptides were injected into Lewis rats and the development of uveitis was monitored clinically and histologically, and IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Rats immunized with HSP peptides that developed uveitis showed significantly higher serum IgG antibody levels to peptide 311–326 (P<0.05) and the corresponding homologous human peptide 336–351 (P<0.01) than rats without uveitis. Significant increases in serum IgA antibodies in rats with uveitis were also observed in those immunized with peptides 111–125, 311–326 and 336–351 (P<0.05). Rats injected with HSP 65 kD showed a rise in IgG antibody levels to peptides 111–125, 154–172 and 311–326 and to a lesser extent, a rise in IgA antibody level to peptide 311–326. HSP showed almost complete inhibition of binding of IgG antibodies to HSP 65 kD, but peptides 111–125, 154–172, 311–326 and 336–351 showed inhibition to a lesser extent in a competitive assay. These results suggest that increases in IgG and IgA antibody levels to specific peptides within HSP, develop in rats with uveitis. The T and B cell epitopes responsible for the development of ocular disease in rats immunized with HSP-derived peptides, appear to be similar or identical to those found in patients with the ocular type of BD.