CHARACTERIZATION OF IMMUNE RESPONSES TO RETINAL SPECIFIC ANTIGENS

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One of the characteristics of S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP), which are retinal-specific antigens, is th ability to induce an intense autoimmune inflammation in the eyes of experimental animals when injected in the presence of an adjuvant. This disease, called experimental autoimmune uveitis (EAU), is critically depend t on T cells and antigen processing by appropriate antigen-presenting cells (APCs). Antigen processing, which occurs within the endocytic vesicles of the APCs, results in the production of small polypeptide subunits. These small polypeptides must then be protected from further degradation and transported to the cell surface where the interaction with the T cell takes place. In FY 1994 we further characterized the intracellular protein first identif d in FY 1993. We confirmed that the protein does belong to the heat shock family of proteins by partial amino acid sequencing of the 70kD peak. We also identified the peak at 40kD as being actin. Testing with different peptide moieties has shown that binding of immunogenic peptides by hsp70 is a selective process. Certain peptides bind well to hsp70, although othe peptides have no affinity for hsp70. The process is also selective in that it requires ATP in order to release the bound peptide. We have also found increased levels of hsp antibody in the serum of patients with Behcet's disease. The increase serum levels corresponded to periods of ocular inflammatory activity in the absence of any evidence of active systemic disease.