The presence of a cell-mediated immune response to autoantigens proves to be paramount in the pathogenesis of IDDM. Phogrin, a secretory granule protein tyrosine phosphatase (PTPase) found in pancreatic islets, is a potential autoimmune target. Phogrin is known to contain two epitopes, peptide 2 (aa 640-659) and 7 (aa 755-777), in its COOH terminal that lead to T-cell stimulation. We evaluate the possibility of additional epitopes of interest in the intracellular domain by comparing T-cell proliferation responses to phogrin, receptor PTPase rho (RPTPrho) and two chimeric protein derivatives as antigens. This project predicts that peptide 2 and 7 deficient proteins will show little or no T-cell proliferation. Male NOD mice were immunized by injection with recombinant phogrin and T-cells were obtained from sacral, lumbar and inguinal lymph nodes. Bone marrow-derived dendritic cells (DCs) were isolated and matured by the addition of fixed, autoantigen-producing bacteria. Phogrin specific CD-4+ T-cells were co-cultured with mature irradiated DCs for three days. Tritiated thymadine was added during the last 8 hours of incubation to quantify T-cell proliferation. T-cell stimulation was observed in response to phogrin-specific epitopes and chimeric protein lacking peptides 2 and 7. The results suggest the possibility of additional epitopes of interest in the intracellular domain of Phogrin.