CHARACTERIZATION OF MONOCLONAL-ANTIBODIES DERIVED FROM LYMPHOCYTES FROM GRAVES-DISEASE PATIENTS IN A CYTOCHEMICAL BIOASSAY FOR THYROID STIMULATORS

Monoclonal antibodies 208F7 and 307H6, derived from Graves'' lymphocytes, stimulate thyroid function. These antibodies were characterized in the ultrasensitive cytochemical bioassay for thyroid stimulators. Bell-shaped dose-response curves were obtained for both antibodies, confirming their actions as thyroid stimulators; 307H6 was 107 times more potent than 208F7, and the ascending limb of the response curve to 307H6 was not significantly different from that of a reference preparation of thyroid-stimulating antibodies, namely long acting thyroid stimulator-B. Stimulation by both 208F7 and 307H6 was inhibited by antihuman, but not antimouse, Ig. Stimulation by 208F7, but not 307H6, was inhibited by 11E8 (a monoclonal antibody raised against the TSH receptor), which is a relatively potent inhibitor of TSH, but not thyroid-stimulating antibodies. These findings together with previous observations on the interactions of 208F7 and 307H6 with thyroid cells in both the presence and absence of TSH and of 208F7 and 307H6 with solubilized thyroid membrane components are summarized in a model relating the appropriate epitopic regions of the TSH receptor.