Insulin is arguably the “number one” autoantigen in the NOD model of T1D, not only because of its expression restricted to beta cells, the association of its genetic polymorphism with disease risk, and the role of its recognition in initial triggering of the autoimmune response38 but also because the structural basis of its recognition by CD4+ T cells is well understood and provides more evidence for the key role of unusual TCR-pMHC interactions in T1D. The gene discussed is CD4; the disease is type 1 diabetes mellitus.