We have previously shown that the frequency of proinsulin-specific CD4 T cells in peripheral blood of T1D subjects and healthy controls is higher in DRB1*04:01 subjects homozygous for INS VNTR class I as compared with DRB1*04:01 T1D and healthy controls with INS VNTR class III [7], consistent with a mechanism for the protective effect of the class III alleles, involving more efficient deletion of INS-autoreactive T cells, a process known to be antigen dose dependent [8], [9]. This evidence concerns the gene INS and type 1 diabetes mellitus.