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Identification of the Peptides That Inhibit the Function of Human Monoclonal Thyroid-Stimulating Antibodies from Phage-Displayed Peptide Library¹

Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (C.H.B., C.-B.C.), Pohang 790-784, South Korea; Center for Neurologic Disease, Harvard Institute of Medicine, Brigham and Women’s Hospital and Harvard Medical School (J.Y.P.), Boston, Massachusetts 02215; and Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine (T.A.), Kyoto 606-8507, Japan

Address all correspondence and requests for reprints to: Dr. Chi-Bom Chae, Division of Molecular and Life Sciences, POSTECH, Pohang 790-784 Korea. E-mail: cbchae{at}postech.ac.kr

Abstract

Autoantibodies against TSH receptor (TSHR) are known to be involved in the occurrence of Graves’ disease. It is obvious that mapping of epitopes of the autoantibodies found in the patients with Graves’ disease is an important step in elucidating possible mechanism of generation of the autoantibodies against TSHR as well as in developing effective diagnostic and therapeutic approaches for Graves’ disease.

In this report we have identified the peptide sequences that bind to two human monoclonal thyroid-stimulating antibodies (mTSAbs; B6B7 and 101–2) from a disulfide-constrained phage-displayed peptide library. The peptides selected by three rounds of biopanning showed half-maximal inhibitory activities for cAMP synthesis induced by mTSAbs at about 0.1 µmol/L. SPWTLGA and TQWNMQH selected for B6B7 and 101–2, respectively, show specificity for their respective antibodies. This means that different clones of mTSAbs may have different epitopes for TSHR. The IgG of the patient from whom B6B7 was derived binds with specificity to the respective immobilized peptide in an enzyme-linked immunosorbant assay format, and its cAMP generation was also inhibited by selected peptide. It may be possible that the epitopes of TSAbs identified from the phage-displayed peptide library could be used for the classification of different clones of TSAbs present in patients with Graves’ disease and for development of drugs to treat Graves’ disease.

This article has been cited by other articles:

				C. H. Na, M. H. Lee, B. Y. Cho, and C.-B. Chae A Method for Identification of the Peptides That Bind to a Clone of Thyroid-Stimulating Antibodies in the Serum of Graves' Disease Patients J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1570 - 1576. [Abstract] [Full Text] [PDF]