Pathogenic Thyroglobulin Peptides as Model Antigens: Insights on the Induction and Maintenance of Autoimmune Thyroiditis

Abstract

In recent years, the discovery of pathogenic thyroglobulin (Tg) peptides has given a new impetus to study, at the basic level, mechanisms of induction and immunoregulation of autoimmune thyroiditis. The genetic control of the immune response against defined Tg epitopes and the diversity of the T-cell receptor repertoire recruited for their recognition were among the first issues examined. Some of these epitopes contained hormonogenic sites, i.e. thyroxine residues, and thus offered an excellent opportunity to study how post-translational modifications such as iodination, can influence induction of thyroiditogenic cells. The delineation of pathogenic Tg determinants also enabled the search for “molecular mimics” i.e. peptides of microbial origin that may be involved in the pathogenesis of the disease. In addition, factors promoting the generation of pathogenic epitopes during Tg processing in antigen presenting cells could now be systematically investigated. This review summarizes recent findings in these areas.