With that in mind, we and others developed insulin B10-23:MHC Class II tetramer reagents [20–23] to track insulin-specific CD4+ T cells during disease development and at onset in NOD mice, as well as interrogate the fate of this population in diabetes resistant B6.I-Ag7 (B6.g7) mice to understand tolerance mechanisms in play [24, 25]. This evidence concerns the gene INS and diabetes mellitus.