Recombinant Human Antibody (K1-70) is capable of binding to TSH receptor (TSHR), expressed in HEK 293 cells. Expressed as the combination of a heavy chain (HC) containing VH from anti-TSH receptor (TSHR) mAb and CH1-3 region of human IgG1 and a light chain (LC) encoding VL from anti-TSH receptor (TSHR) proteins mAb and CL of human kappa light chain. Exists as a disulfide linked dimer of the HC and LC hetero-dimer under non-reducing condition. The blocking autoantibody K1-70 binds more N-terminally on the TSHR concave surface than either the stimulating autoantibody M22 or the hormone TSH, and this may reflect its different functional activity.
Figure 1 Crystal structure of TSHR260 in complex with thyroid stimulating monoclonal autoantibody (M22) Fab (TSHR-M22) and with the TSHR blocking monoclonal autoantibody (K1-70) Fab (TSHR-K1-70).
Cartoon diagrams of the complex structures are shown. TSHR is in cyan, light chains are in green and the heavy chains in blue. Disulphide-bonded cysteines are shown as balls and sticks, disulphide bonds are in yellow and cysteine residues are labelled in orange. The N- and C-termini are marked. M22 interactions with TSHR amino acid R255 are marked and shown as balls and sticks. In contrast there are no interactions between K1-70 and amino acid R255 or the C-terminus of the TSHR. Reproduced from Figure 5 of Furmaniak et al. [3] with kind permission from Springer Science and Business Media.
Furmaniak, J., Sanders, J., Miguel, R. N., & Smith, B. R. (2015). Mechanisms of action of TSHR autoantibodies. Hormone and Metabolic Research, 47(10), 735-752.
Figure 2 Bridge type TRAb ELISA using TSHR 260 alkaline phosphatase.
A. Binding of stimulating (K1-18 and M22) and blocking (K1-70) human monoclonal autoantibodies and B binding of K1 donor serum IgG (lower x-axis); NIBSC 90/672 (upper x-axis). K1-18 IgG (♦); K1-70 IgG (▪); M22 IgG (▴); control MAb (5B3 IgG) (×); K1 donor serum (□); NIBSC 90/672 (○).
Smith, B. R., Sanders, J., Evans, M., Tagami, T., & Furmaniak, J. (2009). TSH receptor–autoantibody interactions. Hormone and Metabolic Research, 41(06), 448-455.
Figure 3 Inhibition of porcine TSH (3 ng/mL)-mediated stimulation of cyclic AMP production by TSHR monoclonal antibodies with antagonist activity.
MAb-B2 IgG (m); K1–70 IgG (d); 5C9 IgG (■).
Sanders, J., Miguel, R. N., Furmaniak, J., & Smith, B. R. (2010). TSH receptor monoclonal antibodies with agonist, antagonist, and inverse agonist activities. In Methods in enzymology (Vol. 485, pp. 393-420). Academic Press.
Figure 3 Inhibition of porcine TSH (4 ng/mL)-mediated stimulation of cyclic AMP production by TSHR monoclonal antibodies with antagonist activity.
(A)Human MAb 5C9 (antagonist and inverse agonist; derived from the comparative model of 5C9 structure), (B) mouse MAb-B2 (antagonist; derived from the crystal structure solved at 3.3 A˚ resolution), (C) human MAb K1–70 (antagonist; derived from the crystal structure solved at 2.2 A˚ resolution), (D) human MAb M22 (agonist; derived from the crystal structure solved at 1.65 A˚ resolution). Position of the charged residues is indicated in the figures on the left-hand side of the panel and the position of aromatic
residues is indicated in the figures on the right-hand side of the panel. Acidic patches are shown in red and basic patches in blue (See Color Insert).
Sanders, J., Miguel, R. N., Furmaniak, J., & Smith, B. R. (2010). TSH receptor monoclonal antibodies with agonist, antagonist, and inverse agonist activities. In Methods in enzymology (Vol. 485, pp. 393-420). Academic Press.
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CAT | Product Name | Application | Type |
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MOB-1074z | Mouse Anti-TSHR Recombinant Antibody (clone 9B2) | WB, ELISA, FC, IP, FuncS | Mouse IgG1 |
PABL-353 | Mouse Anti-TSHR Recombinant Antibody (clone 3BD10) | WB, ELISA, FuncS | Mouse IgG |
PABW-172 | Recombinant Human Anti-TSHR Antibody (M22) | WB, ELISA, PK | IgG |
HPAB-0328CQ | Mouse Anti-TSHR Recombinant Antibody (HPAB-0328CQ) | ELISA, FC, Neut, FuncS | Mouse IgG |
HPAB-0329CQ | Mouse Anti-TSHR Recombinant Antibody (HPAB-0329CQ) | ELISA, FC, Neut, Agonist, FuncS | Mouse IgG |
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