Am. Saboori et al., IODINATION OF HUMAN THYROGLOBULIN (TG) ALTERS ITS IMMUNOREACTIVITY - I - IODINATION ALTERS MULTIPLE EPITOPES OF HUMAN TG, Clinical and experimental immunology, 113(2), 1998, pp. 297-302
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.