The analysis of the structural features of the various HLA-DR4 heterodimers and their potential impact on risk of T1D remains incomplete, as we lack the crucial pieces of information regarding the primacy of certain CD4+ T cell epitopes in the possible etiological establishment and strengthening of the emerging autoimmune reactions (firstly manifested as seroconversion), and then in the variable length prodrome of pathogenesis finally leading to clinical T1D. This evidence concerns the gene CD4 and type 1 diabetes mellitus.