Given the high degree of homology between proinsulin 1 and 2 proteins, especially in the immunodominant insulin B chain epitope Ins B:9-23 we expected to achieve robust protection from diabetes onset in TIP-1 mice, similar to previously described proinsulin-2 tolerant NOD mice (35); however, the partial protection from insulitis and diabetes observed in TIP-1 mice points to the existence of distinct pathogenic peptide epitopes in the PIns2 protein that can precipitate autoimmunity in NOD mice. This evidence concerns the gene INS and Autoimmunity.