Immunoinformatic Analysis of Human Thyroglobulin

Abstract

Abstract The AutoImmune ThyroiDitis (AITD), known as Hashimoto’s disease, is a chronic autoimmune thyroid disease progressively developed to hypothyroidism. The AITD is characterized by the formation of autoantibodies targeting two specific thyroid antigens, Thyroglobulin (Tg) and Thyroid PerOxidase (TPO). Tg is a precursor of the thyroid hormones while TPO catalyses their synthesis. The AITD has a strong genetic predisposition. During the last years, it was found that the susceptibility to AITD is associated with certain Human Leukocyte Antigens (HLA) class II genes of loci DR and DQ. In the present study, we applied in-house immunoinformatic tools to identify peptides originating from Tg and binding to AITD susceptible alleles: HLA-DR3, HLA-DR4, HLA-DR5, HLA-DQ2 and HLA-DQ8. Five peptide fragments containing promiscuous overlapping binders were selected. These were p470, p949, p1948, p2348 and p2583. Only one of them contains a known epitope (p1948). The rest have not been reported yet. The selected peptide fragments will be coupled to monoclonal antibodies specific to inhibitory B cell receptors designed to suppress the production of Tg autoantibodies.