GAD65 and insulin B chain peptide (9-23) are not primary autoantigens in the type 1 diabetes syndrome of the BB rat

To investigate whether GAD(65) whole molecule, GAD(65) p(35) Or insulin B chain peptide (amino acids 9-23) play an essential role in the pathogenesis of type 1 diabetes in the BioBreeding (BB) rat, we gave serial injections of GAD(65), p35 or insulin B chain (9-23) to six groups of BB/Worcester rats. The individual antigens mere administered either intrathymically on day 2 and intraperitoneally in MF 59-0 adjuvant 5 times during the first 5 weeks, or by intranasal instillation once neonatally and 5 days/week for the following 6 weeks, Control groups were injected with vehicle only, Age of onset of diabetes and degree of insulitis mere not different between controls and antigen-treated rats, Rats that received GAD(65) intrathymically and intraperitoneally developed high GAD(65)-antibody titers without altering diabetes development, In GAD(65)-treated animals, serum antibodies recognized epitopes at 3 sites on GAD(65) in diabetic animals but only at 1 site in non-diabetic animals, GAD(65)-injected animals also showed a significant reduction of IFN-gamma mRNA expression in the thymus, This study provides evidence against the hypothesis that GAD(65) and insulin B chain peptide (9-23) are primary diabetogenic autoantigens in BE rats because immunizations with these antigens and GAD(65)-induced immune deviation did not alter the development of diabetes.