Mapping the autoepitopes of thyroglobulin

Chronic thyroiditis is currently the best available model of an organ-restricted autoimmune disease, because the principle antigen Tg is a well-characterized protein and the disease can be reproduced by experimental immunization. The pattern of autoantigenic determinants of Tg that is recognized by sera from subjects without detectable thyroid disease is clearly different from that seen with thyroiditis patients. Both sets of sera react with the evolutionary conserved portions, the hormonogenic regions containing the T3 and T4 moieties. Sera of thyroiditis patients, however, also react with the evolutionary variable, species-specific portions of the Tg molecule. Mice immunized with human Tg respond to the same, immunodominant sites. Mice injected with mouse Tg preferentially recognize the analogous, mouse-specific sites of Tg. Mice are not restricted, however, in their use of V-(D)-J genes for Ig production, even when the same antigenic determinant is involved.