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 (T4) and triiodothyronine (T3), is one of the major autoantigens in autoimmune thyroiditis. The degree of iodination of Tg may have a major impact on its immunological properties by changing its antigenicity with respect to antibody binding. We have previously prepared a panel of MoAbs that bind to different epitopes of the Tg molecule. In the present study, we show that iodination alters the conformation of Tg molecule in such a way that it is recognized differently by different MoAbs. Monoclonal antibody 137C1 recognizes Tg regardless of its iodine content. Monoclonal antibody 42C3 recognizes Tg only if the Tg is iodinated either in vitro or in vivo. Monoclonal antibody 133B1 recognizes both in vivo iodinated Tg and non-iodinated Tg, but this MoAb did not recognize Tg following in vitro iodination. Monoclonal antibody 41A5 recognizes 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 conclude that iodination of Tg by either in vivo or in vitro methods changes its conformation in such a way that some natural epitopes are 'lost' and some 'new' epitopes are generated. The generation of new epitopes may be important in the generation of autoimmune responses leading to autoimmune disease.
Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205-2196, USA.
A M
AM
Saboori
N R
NR
Rose
H S
HS
Bresler
M
M
Vladut-Talor
C L
CL
Burek
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D018604:Epitope Mapping; D006801:Humans; D007455:Iodine / Q000276:immunology*; D011487:Protein Conformation; D013954:Thyroglobulin / Q000031:analogs & derivatives / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D013954:Thyroglobulin; D007455:Iodine