Anti-Human TSHR (Clone M22) – Purified No Carrier Protein

Isolated lymphocytes from a patient with Graves' disease

This recombinant monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

Antibodies may be stored sterile as received at 2-8°C for up to one year. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≥ -80°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

M22 activity is directed against human TSHR (thyroid-stimulating hormone receptor).

Graves’ disease is an autoimmune disease that can cause hyperthyroidism with TSH receptor (TSHR) autoantibodies (TRAbs) playing a key role in its pathogenesis¹. There are two types of TRAbs, both of which inhibit thyroid-stimulating hormone (TSH) binding to its receptor TSHR: 1) stimulating TRAbs (TSHR agonists) which bind to the TSHR and mimic the biological activity of TSH by stimulating the cyclic AMP pathway and thyroid hormone synthesis and 2) blocking TRAbs (TSHR antagonists) which bind to the receptor but do not activate the cyclic AMP pathway.

M22 is a thyroid-stimulating monoclonal antibody that was obtained from the peripheral blood lymphocytes of a 19-year-old male with Graves’ hyperthyroidism and type-1 diabetes mellitus^1,2,3. M22 was generated by infecting lymphocytes with Epstein-Barr virus and fusing with mouse/human hybrid cell line K6H6/B5^2,3. M22-TSHR crystal structure and mutation experiments have shown that M22 interacts with a number of TSHR residues, some of which affect the biological activity of M22 when mutated¹. Additionally, structural analysis has shown that M22 pushes the extracellular domain of TSHR into an upright active conformation in a manner similar to its natural ligand TSH⁴.

M22 strongly inhibits TSH binding to TSHR and is a potent thyroid stimulator (TSHR agonist), as determined by its ability to stimulate cyclic AMP production in Chinese hamster ovary cells^2,5. M22 can also act as an autoantibody to activate TSHR, causing abnormal production of thyroid hormones⁴. The utility of M22 in CAR-T cell therapy of thyroid cancer is being investigated⁶.

TSHR is primarily found on the surface of thyroid epithelial cells. TSHR can also be found on adipose tissue, fibroblasts, the anterior pituitary gland, hypothalamus, and kidneys.

1 Furmaniak J, Sanders J, Rees Smith B. Auto Immun Highlights. 4(1):11-26. 2012.
2 Sanders J, Evans M, Premawardhana LD, et al. Lancet. 362(9378):126-128. 2003.
3 Sanders J, Miguel RN, Furmaniak J, et al. Methods Enzymol. 485:393-420. 2010.
4 Duan J, Xu P, Luan X, et al. Nature. 609(7928):854-859. 2022.
5 Sanders J, Jeffreys J, Depraetere H, et al. Thyroid. 14(8):560-570. 2004.
6 Li H, Zhou X, Wang G, et al. J Clin Endocrinol Metab. 107(4):1110-1126. 2022.
7 Tonacchera M, Ferrarini E, Dimida A, et al. Thyroid. 16(11):1085-1089. 2006.
8 Kumar S, Schiefer R, Coenen MJ, et al. Thyroid. 20(1):59-65. 2010.
9 van Zeijl CJ, van Koppen CJ, Surovtseva OV, et al. J Clin Endocrinol Metab. 97(5):E781-5. 2012.