The etiology of autoimmunity diseases includes an immunological reaction against various autoantigens. The HLA molecules play an important role in the antigen presentation process to the immune system. The HLA genes were found as the most significant genetic predisposition factor. The strongest association described in the literature is the association of HLA-B27 with ankylosing spondylitis. Associations were since usually observed with HLA-DR and DQ genes. We are also focused on Diabetes mellitus 1. type. Diabetes is an organ specific autoimmune disease characterised by destruction of beta-cells of Langerhansen pancreatic islets. The cause of the destruction process is not known yet, but it seems to be triggered by repeated presentation of self-antigen hGAD65 to the immune system. This review presents the most interesting solutions and hypotheses of the unanswered question about HLA association mechanism.