The cryptic self in thyroid autoimmunity: the paradigm of thyroglobulin

Recent studies have increased the number of known thyroiditogenic sites in thyroglobulin (Tg) to thirteen. These sites contain T-cell epitopes and are scattered throughout Tg, with nine of them localized toward the carboxyl terminal third of the molecule. So far, no pathogenic determinant has been found to be dominant, i.e. to be readily and consistently generated in extrathyroidal antigen-presenting cells (APC) following processing of intact Tg in vivo and in vitro. However, certain conditions, such as internalization of Tg-antibody complexes or enhanced iodination of Tg, have been described to promote generation of cryptic pathogenic peptides in APC, in vitro. These findings support the view that post-translational events can "unmask the cryptic self' and suggest mechanisms that may contribute to the pathogenesis of thyroiditis.