The definitive evidence was obtained using NOD mice containing a transgene coding a mutant insulin B chain with a tyrosine to alanine change at the 16th position (referred to as B16A).30 This mutation maintained bioactivity of the insulin molecule; however, development of IAAs, insulitis, and clinical diabetes was completely suppressed.30 By contrast, the T cells in the B16A mice were able to reject normal islets expressing wild-type insulin.31 Therefore, without recognition of a small fragment of the insulin B chain, reactivity to other antigens cannot elicit effective pathogenic responses. The gene discussed is INS; the disease is diabetes mellitus.