A monoclonal thyroid-stimulating antibody

The thyrotropin receptor, also known as the thyroid-stimulating hormone receptor (TSHR), is the primary antigen of Graves disease.Stimulating TSHR antibodies are the cause of thyroid overstimulation and were originally called long-acting thyroid stimulators due to their prolonged action.Here we report the successful cloning and characterization of a monoclonal antibody (MS-1) with TSHR-stimulating activity.The thyroid-stimulating activity of MS-1 was evident at IgG concentrations as low as 20 ng/ml.MS-1 also competed for radiolabeled TSH binding to the native TSHR and was able to compete for TSH-induced stimulation.MS-1 recognized a conformational epitope within the TSHR (or A) subunit but excluding the receptor cleavage region.Using an assay measuring loss of antibody recognition after cleavage we demonstrated that MS-1, in contrast to TSH, was unable to enhance TSHR posttranslational cleavage.Since receptor cleavage is followed by subunit shedding and receptor degradation, the functional half-life of the receptor may be extended.The isolation and characterization of MS-1 provides a novel explanation for the prolonged thyroid stimulation in this disease which may be secondary to the lack of receptor cleavage in addition to the prolonged half-life of IgG itself.