Neonatal Fc receptor - an IgG Fc fragment receptor , the product of the human gene FCGRT [1] [2] . This is a heterodimeric receptor consisting of a heavy chain with MHC I -like folding and microglobulin β2. The receptor recognizes the site that connects the C H 2 and C H 3 domains of IgG, which distinguishes it from the classical Fc receptor γ and the component of the C1q complement system and brings it closer to bacterial proteins A and G , which bind to the same site. In the early stages of an organism's life, the neonatal Fc receptor provides for the uptake of IgG antibodies from the mother’s blood or milk, and in the adult organism it plays an important role in maintaining homeostasis of antibodies of this isotype and serum albumin , protecting them from premature degradation . In humans, this receptor is found in the vascular endothelium , occupational antigen-presenting cells , intestinal epithelium , the central nervous system endothelium, the podocytes of the kidneys and the lungs [3] .
Fc fragment of IgG, receptor, transporter, alpha | |
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Legend | |
Characters | FCGRT |
Entrez gene | 2217 |
Hgnc | 3621 |
OMIM | 601437 |
Refseq | NM_004107 |
UniProt | P55899 |
Other data | |
Locus | 19th hr. , 19q13.3 |
FcRn was first discovered in rodents. This unique receptor carried IgG from human milk through the intestinal epithelium into the blood of newborn rodents [4] . Studies have confirmed the existence of such a receptor in humans. A human neonatal Fc receptor is found in placental syncytiotrophoblasts, where it facilitates the transport of maternal IgG to the fetal bloodstream. FcRn binds IgG at an acidic pH of about 6.0–6.5, but not at neutral or higher pH values. Thus, FcRn binds IgG in the intestinal lumen at slightly acidic pH values and provides unidirectional transport of immunoglobulins to the basolateral membrane of intestinal cells, where the medium is neutral or alkaline (pH 7.0-7.5).
This receptor also plays a role in the utilization of IgG in the adult organism, as it participates in endocytosis in endothelial cells. In acidic endosomes, the neonatal Fc receptor binds IgG, which has been internalized as a result of pinocytosis , provides protection against lysosomal degradation, transfer to the cell surface and release into the alkaline environment of the blood. This mechanism may explain the longer duration of the half-life of IgG compared with antibodies of other isotypes [5] . In the same way, through acidic endosomes, the transfer of maternal IgG captured by syncytiotrophoblasts during pinocytosis to the side of the fetus occurs [3] .
It is known that conjugation of some drugs with the IgG Fc fragment significantly increases their half-life. It is likely that the stability of drugs is ensured by the same mechanism as the stability of the IgG itself [6] . To date, 5 types of drugs are available that use an IgG Fc fragment to increase stability: aflibercept, alephacept , rilonept , etanercept , romiplostim and abatacept .
Notes
- -Story CM, Mikulska JE, Simulator NE, I-like Fc receptor cloned from human placenta: Journal of Experimental Medicine : journal. - Rockefeller University Press , 1994. - December ( vol. 180 , no. 6 ). - P. 2377–2381 . - DOI : 10.1084 / jem.180.6.2377 . - PMID 7964511 .
- ↑ Kandil E., Egashira M., Miyoshi O., Niikawa N., Ishibashi T., Kasahara M., Miyosi O. I-like Fc receptor (FCGRT) maps to 19q13.3 (Eng.) // Cytogenetic and Genome Research : journal. - Karger Publishers , 1996. - Vol. 73 , no. 1-2 . - P. 97-8 . - DOI : 10.1159 / 000134316 . - PMID 8646894 .
- ↑ 1 2 Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age (Neopr.) // Nat Rev Immunol .. - 2007. - V. 7 , No. 9 . - p . 715-725 . - DOI : 10.1038 / nri2155 . - PMID 17703228 .
- ↑ Jones EA and Waldman TA (1972) The mechanism of intestinal transgular transport of IgG in the neonatal rat. J Clin Invest, 51, 2916.
- ↑ Goebl NA, Babbey CM, Datta-Mannan A., Witcher DR, Wroblewski VJ, Dunn KW Neonatal Fc Receptor Medium Cells (English) // Molecular Biology of the Cell : journal. - 2008. - December ( vol. 19 , no. 12 ). P. 5490-5505 . - DOI : 10.1091 / mbc.E07-02-0101 . - PMID 18843053 .
- ↑ Lee TY, Tjin Tham Sjin RM, Movahedi S., Ahmed B., Pravda EA, Lo KM, Gillies SD, Folkman J., Javaherian K. Linking the antibody to endostatin half-life and efficacy (eng. ) // Clinical Cancer Research : journal. - 2008. - March ( vol. 14 , no. 5 ). P. 1487–1493 . - DOI : 10.1158 / 1078-0432.CCR-07-1530 . - PMID 18316573 .