Like most cancers, autoimmune diseases generally are due to the intera
ction of a number of genetic traits with an environmental trigger. Aut
oimmune thyroiditis, a model of organ-specific autoimmune disease, is
associated with iodine as a precipitating environmental factor. T cell
s from patients with chronic thyroiditis proliferate in response to no
rmal human thyroglobulin, but fail to react with non-iodinated thyrogl
obulin. Using a selected monoclonal antibody, we were able to identify
a binding site on thyroglobulin containing iodinated thyronine. The g
reatest affinity was for tetraiodothyronine and binding depended upon
the number as well as the positions of iodines. We have also studied a
n inbred strain of mice, NOD-H2(h4), that developed thyroiditis sponta
neously. The onset of disease was hastened in a dose-dependent manner
by adding iodine to the drinking water. The occurrence of disease was
greater in conventional than in specific pathogen-free mice and correl
ated with T-cell proliferation and IgG(2b), antibody to thyroglobulin.