The influence of normal human IgG and of thyroid-stimulating antibody (TSAb) on the binding of thyrotropin to thyroid plasma membranes.

The influence of serum IgG from normal and Graves' disease subjects on the binding of 125I-thyrotropin to isolated thyroid membranes was studied. IgG from either source inhibited binding in a concentration -dependent fashion. Human membranes were more sensitive to the human IgG than were bovine thyroid membranes and, when membranes were purified by discontinuous sucrose gradient centrifugation, they were more sensitive than were those less-purified, obtained by differential centrifugation. Using a Dixon plot, inhibition by normal IgG showed non-competitive kinetics. Fab fragments were more effective, on an equimolar basis, than was intact normal IgG, but were less potent when Graves' disease IgG was the parent molecule; this difference implies distinct modes of inhibition of thyrotropin-binding. The degree of inhibition by normal IgG was variable so that multiple control preparations are required to assess the additional effect characteristic of IgG from the subject with Graves' disease.