Using a preproinsulin peptide library, immunodominant epitopes located within the C peptide (C13-29) and B chain (B11-27) were preferentially recognized by CD4+ T cells from autoantibody positive individuals at high risk for T1D development whereas CD4+ T cells from insulin-treated T1D patients were responsive to native insulin and insulin B chain (B1-16). This evidence concerns the gene INS and type 1 diabetes mellitus.