Recognition of Thyroglobulin by T Cells: The Role of Iodine

Among known autoantigens, thyroglobulin (Tg) is unique in its capacity to store iodine, an element provided in our daily diet. Evolutionary pressure has sculpted Tg into a large molecular scaffolding to allow organification of iodide and its incorporation into thyroid hormones. The increase in molecular size and the posttranslational modification by iodine had to exact immunological consequences. Over the last 15 years, numerous Tg peptides-targets of thyroiditogenic T cells-have been mapped, raising questions regarding the mechanisms that maintain or abrogate immune tolerance against this large autoantigen. This review summarizes the work in this area and discusses the role iodine may play in these processes.