IODINATION OF HUMAN THYROGLOBULIN (TG) ALTERS ITS IMMUNOREACTIVITY - I - IODINATION ALTERS MULTIPLE EPITOPES OF HUMAN TG

Human Tg, the site of synthesis of thyroid hormones, thyroxine (TI) an d triiodothyronine (T3), is one of the major autoantigens in autoimmun e thyroiditis. The degree of iodination of Tg may have a major impact on its immunological properties by changing its antigenicity with resp ect to antibody binding. We have previously prepared a panel of MoAbs that bind to different epitopes of the Tg molecule. In the present stu dy, we show that iodination alters the conformation of Tg molecule in such a way that it is recognized differently by different MoAbs. Monoc lonal antibody 137C1 recognizes Tg regardless of its iodine content. M onoclonal antibody 42C3 recognizes Tg only if the Tg is iodinated eith er in vitro or in vivo. Monoclonal antibody 133B1 recognizes both in v ivo iodinated Tg and non-iodinated Tg, but this MoAb did not recognize Tg following ii; vitro iodination. Monoclonal antibody 41A5 recognize s intact Tg and tryptic peptides of normal (in vivo) iodinated and non -iodinated Tg, but did not bind the tryptic peptides of artificially ( in vitro) iodinated Tg. From the results of these experiments, we conc lude that iodination of Tg by either in vivo or in vitro methods chang es its conformation in such a way that some natural epitopes are 'lost ' and some 'new' epitopes are generated. The generation of new epitope s may be important in the generation of autoimmune responses leading t o autoimmune disease.