Insulin B:9-23-reactive CD4+T cells are present in the peripheral blood of T1D individuals, the immunogenic register of this peptide has low-affinity binding to HLA-DQ8 (ref. 30) and a strong agonistic variant of the natural insulin epitope established in the murine system7 can efficiently stimulate human CD4+T cells31. This evidence concerns the gene INS and type 1 diabetes mellitus.