Searching for pathogenic epitopes in thyroglobulin: Parameters and caveats

Last year marked the 40th anniversary of the discovery that thyroglobulin (Tg) is a major autoantigen in autoimmune thyroiditis. The Tg molecule presents unique challenges for epitope mapping owing to its large size and extensive iodination. Consequently, pathogenic determinants have only recently been identified. Here, George Carayanniotis and Varada Rao summarize the approaches used to determine pathogenic Tg T-cell epitopes and discuss caveats in this unusual quest.