To create the recombinant Macaca fascicularis FCGRT protein, we use genetic engineering techniques to insert a gene fragment that encodes the 24-297aa of Macaca fascicularis FCGRT into E.coli through a plasmid. The N-terminal 6xHis-SUMO-tag gene is also cloned into the plasmid. The E.coli serves as a factory for producing the recombinant FCGRT protein using its cellular machinery. The resulting products undergo affinity chromatography purification, reaching a purity of over 90% as measured by SDS-PAGE.
The FcGRT protein is a critical component of the neonatal Fc receptor (FcRn), which is significant in regulating immunoglobulin G (IgG) and albumin levels in the bloodstream. It is structurally similar to MHC class I molecules and is essential for IgG recycling, extending its half-life in circulation. The FCGRT gene is located on chromosome 19q13.35 and exhibits polymorphisms that can influence the expression levels of the FcRn protein, which in turn affects immune responses and susceptibility to various diseases, including autoimmune disorders and cancers [1][2][3].
FcGRT functions primarily by binding to IgG in acidic endosomal compartments, allowing for the recycling of IgG back to the extracellular space, which prevents its degradation in lysosomes [4][5]. This mechanism is important in maintaining IgG levels during immune responses, as it allows for the sustained presence of antibodies in circulation, which is crucial for effective immune surveillance and response [6]. Increased expression of FcGRT has been associated with certain cancers, such as glioma, where it mediates the malignant phenotype by prolonging IgG half-life and enhancing immune evasion [4].
References:
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[2] A. Fisse, Association of the neonatal fc receptor promoter variable number of tandem repeat polymorphism with immunoglobulin response in patients with chronic inflammatory demyelinating polyneuropathy, European Journal of Neurology, vol. 31, no. 4, 2024. https://doi.org/10.1111/ene.16205
[3] M. Dalakas and P. Spaeth, The importance of fcrn in neuro-immunotherapies: from igg catabolism, fcgrt gene polymorphisms, ivig dosing and efficiency to specific fcrn inhibitors, Therapeutic Advances in Neurological Disorders, vol. 14, p. 175628642199738, 2021. https://doi.org/10.1177/1756286421997381
[4] G. Wang, Z. Wang, T. Ma, J. Pan, H. Ge, T. Yanet al., Fcgrt, a cancer-derived immunoglobulin g binding protein, mediates the malignant phenotype of glioma,, 2023. https://doi.org/10.21203/rs.3.rs-3217723/v1
[5] M. Babamohamadi, Anti-ctla-4 nanobody as a promising approach in cancer immunotherapy, Cell Death and Disease, vol. 15, no. 1, 2024. https://doi.org/10.1038/s41419-023-06391-x
[6] M. Pyzik, L. Kozicky, A. Gandhi, & R. Blumberg, The therapeutic age of the neonatal fc receptor, Nature Reviews Immunology, vol. 23, no. 7, p. 415-432, 2023. https://doi.org/10.1038/s41577-022-00821-1
