Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different - Evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes

Two rodent models of autoimmune type 1 diabetes have been used to investiga te the role of insulin as an autoantigen in this disease. In lymphopoenia-i nduced diabetes in the PVG.RT1(u) rat, neonatal tolerization with insulin B -chain peptides, but not A-chain peptides, conferred significant protection from disease. After rechallenge of adult rats, neonatally B-chain-tolerize d animals showed diminished B-chain-specific T-cell proliferation, interleu kin (IL)-2 production, and interferon-gamma (IFN-gamma) production, as comp ared with control animals. The epitope recognized by the PVG.RT1(u) rat was mapped to residues 1-18 of the B-chain; T-cell Lines specific for this epi tope were generated, and these conferred diabetes upon adoptive transfer to irradiated syngeneic recipients. In adult nonobese diabetic (NOD) mice, su bcutaneous immunization with B-chain peptide 9-23 emulsified in incomplete Freund's adjuvant (IFA) was also potent at preventing onset of diabetes. In contrast to PVG.RT1(u) rats, NOD mice recognized an epitope within residue s 10-29 of the insulin B-chain. The data implicate insulin as a target auto antigen in type 1 diabetes but do not support a role for molecular mimicry to insulin in the pathogenesis of this disease.