Generation and characterization of monoclonal antibodies to the human thyrotropin (TSH) receptor: antibodies can bind to discrete conformational or linear epitopes and block TSH binding

Endocrinology
G S SeetharamaiahB S Prabhakar

Abstract

Splenocytes from female BALB/c mice immunized with a recombinant extracellular domain of the human TSH receptor (ETSHR) were used to generate a panel of 23 hybridomas that produce TSHR-specific monoclonal antibodies (mAbs). All mAbs were of the immunoglobulin G (IgG) isotype and belonged to different subclasses, including IgG1, IgG2a, and IgG2b. The antibodies bound to the ETSHR with relatively high affinity, and several of them blocked the binding of [125I]TSH to the TSHR, with some showing better blocking than others. Competitive binding studies with a subgroup of 4 biotinylated mAbs showed at least 3 different binding specificities. To determine the TSHR epitopes to which these mAbs were binding, we tested them against 37 overlapping synthetic peptides that span the entire ETSHR. mAb 47, which did not block TSH binding, bound to an epitope represented by amino acid residues 22-30. mAb 28, which had a TSH binding inhibitory index of 20%, bound to an epitope represented by amino acids 32-41. However, mAbs 37 and 49, with TSH binding inhibitory index values of 39% and 43%, respectively, showed no significant reactivity with any of the peptides, suggesting that they react with a conformational epitope. Together, these studies sh...Continue Reading

Citations

Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·N ShimojoK Tahara
Jul 30, 2005·Clinical & Developmental Immunology·Takao Ando, Terry F Davies
Aug 22, 2006·Journal of Immunological Methods·Heiko AndresenOliver J Kreuzer
Oct 31, 2001·Clinical Immunology : the Official Journal of the Clinical Immunology Society·S RaoM J Holterman
Oct 1, 2011·The Journal of Clinical Endocrinology and Metabolism·Akira KawashimaKoichi Suzuki
Apr 14, 2005·Endocrine Reviews·Sandra M McLachlanBasil Rapoport
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Feb 18, 2010·Expert Review of Endocrinology & Metabolism·Susanne NeumannMarvin C Gershengorn
Jan 1, 1996·Autoimmunity·G S SeetharamaiahB S Prabhakar

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