Fc receptors (FcRs) are membrane molecules expressed by several hematopoietic cells that recognize the Fc region of several immunoglobulin (Ig) classes and subclasses. Immunoglobulins (Igs) are glycoproteins that have same chemical structures as antibody molecules. Igs is a tetrapeptide chain structure composed of two identical light and two identical heavy chains, connected by interchain disulfide bonds. There are five main types of Igs expressed in the human body: IgM, IgA, IgD, IgG and IgE, with the highest abundance of IgG.

Furthermore, IgG-based antibodies are the only therapeutic antibody based products in the market at present. Communication of IgG antibodies with the immune system is controlled and mediated by Fc gamma receptors (FcγRs), membrane-bound proteins, which relay the information sensed and gathered by antibodies to the immune system.

In terms of the antibody's action mechanism, the antibody is composed of an antigen binding site (Fab) and a crystallizable site (Fc). The Fab segment can bind to a specific antigen, thereby determining the specificity and affinity of the antibody; the Fc segment of IgG can bind to Fc receptors (FcγRI, FcγRII, FcγRIII) expressed on the surface of immune cells, complement (C1q) and FcRn (neonatal FcR) in the blood, thereby activating the immune effect.

It is worth noting that the interaction mediated by the antibody Fc domain can strongly influence the functional outcome of antibody therapy including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC) through the interaction of the Fc domain with Fc receptors on different cell types.

Fc-mediated interaction: ADCC, ADCP and CDC

ADCC: The antibody first binds to the target on the tumor cell, and then the Fc part is recognized by the FcγR on the effector cell. Fc and FcγR activate effector cells, leading to the release of molecules contained in cytotoxic granules, such as perforin, granulysin and granzyme, leading to the lysis of tumor cells. The ability of therapeutic antibodies to induce ADCC depends on their binding affinity to the target and activated FcγR.

ADCP: ADCP is also an important mechanism for recognizing and mediating the effect of therapeutic antibodies on tumor cells. Contrary to ADCC, ADCP mainly works by NK cells expressing FcγRIIIa. In addition, ADCP can also be expressed by monocytes, macrophages, neutrophils and dendritic cells by expressing FcγRIIa (CD32a), FcγRI (CD64) and FcγRIIIa (CD16a) to mediate. In macrophages, the expression levels of these receptors are highly dynamic and are affected by factors such as cell, tissue microenvironment and inflammation. These three receptors can participate in antibody recognition, immune receptor aggregation, and mediate the generation of intracellular ADCP signals. Studies have shown that FcγRIIa (CD32a) is the key receptor involved in this process.

CDC: Clq component binding to Fc is a prime initial step of the complement cascade, which ultimately leads to CDC. The classical activation pathway of CDC is triggered when the C1 complex binds to the antibody-antigen complex. As the cascade of complement proteins activates, membrane attack complexes are formed, leading to the lysis of target cells. Three approved anti-cancer antibodies take advantage of this mechanism: rituximab, ofazumab (Arzerra; Genmab/GlaxoSmithKline) and tositumumab (Bexxar; GlaxoSmithKline). Several methods promote the binding of the antibody constant region to C1q successfully enhanced CDC, and engineered amino acid mutations were inserted into the Fc or hinge region, resulting in improved binding of the antibody constant region to C1q.

Half-life: The combination of IgG and neonatal FcR（FcRn） can protect antibodies from being degraded, thereby prolonging the half-life of IgG in serum. Under acidic conditions (pH6.0-6.5), FcRn binds IgG, and dissociation occurs under neutral and weakly alkaline conditions (pH7.0-7.5). Specifically, endothelial cells form endocytosis vesicles by ingesting IgG to form an acidified endosome, and IgG binds to FcRn to form an IgG-FcRn complex. The IgG-FcRn complex is transported to the cell surface through the recirculated endosome. Under physiological conditions such as pH7.4, the IgG-FcRn complex is dissociates, and the IgG is released again into the blood circulation. Through this receptor-mediated recycling mechanism, FcRn effectively protects IgG from lysosomal degradation, thus prolonging the half-life of IgG.

In summary, Fc receptor proteins are of great importance. The Fc domain of an antibody defines its interaction with many immune cells and has become a desired research area. With the increasing understanding of the role of Fc-FcγR, Fc-C1q and Fc-FcRn interactions, antibody engineering efforts promoted to enable exclusive functions. The activity and mechanism of therapeutic antibodies can be enhanced by choosing best Fc. For therapeutic antibody drugs, the binding affinity of candidate antibody drugs and Fc receptor proteins must be characterized to detect the biological activity of the antibody. Further, role of the antibody ADCC/ADCP/CDC/half-life should be analyzed, which has become a crucial step in the process of the development and quality control of antibody drugs.

ACROBiosystems offers a comprehensive collection of high-quality recombinant Fc receptor proteins, including their common variants, to expedite your antibody drug development.

Product list
(All Fc receptors are expressed from HEK293)

• FcRn

• FcγR

• FcεR

Molecule	Cat. No.	Host	Product Description	Structure
FcRn (FCGRT & B2M)	FCM-H5286	HEK293	Human FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Strep II Tag (SPR & BLI & MALS verified)Hot
	FCM-H8286	HEK293	Biotinylated Human FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Strep II Tag, ultra sensitivity (primary amine labeling) (SPR verified)
	FCM-H82W4	HEK293	Biotinylated Human FcRn / FCGRT&B2M Heterodimer Protein,Avitag™,His Tag&Strep II Tag (SPR & BLI & MALS verified)Hot
	FCM-H82W7	HEK293	Biotinylated Human FcRn / FCGRT&B2M Heterodimer Protein, His,Avitag™(MALS & SPR verified)
	FCN-H52W7	HEK293	Human FcRn / FCGRT&B2M Heterodimer Protein, His Tag (SPR & BLI & MALS verified)Hot
	FCM-M52W2	HEK293	Mouse FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Twin-Strep Tag (MALS & BLI verified)
	FCM-M52W8	HEK293	Mouse FcRn / FCGRT&B2M Heterodimer Protein, His Tag (MALS & BLI verified)
	FCM-M82W5	HEK293	Biotinylated Mouse FcRn / FCGRT&B2M Heterodimer Protein, His,Avitag™(MALS & BLI verified)
	FCM-M82W6	HEK293	Biotinylated Mouse FcRn / FCGRT&B2M Heterodimer Protein,Avitag™,His Tag&Twin-Strep Tag (MALS & BLI-verified)
	FCM-R5287	HEK293	Rat FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Strep II Tag (MALS & SPR verified)
	FCM-R82W7	HEK293	Biotinylated Rat FcRn / FCGRT&B2M Heterodimer Protein,Avitag™,His Tag&Strep II Tag (MALS & SPR verified)
	FCM-R52W5	HEK293	Rabbit FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Tag Free (MALS & SPR verified)
	FCM-C5284	HEK293	Cynomolgus / Rhesus macaque FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Strep II Tag (MALS & BLI verified)
	FCM-C52W9	HEK293	Cynomolgus / Rhesus macaque FcRn / FCGRT&B2M Heterodimer Protein, His Tag (MALS & BLI verified)
	FCM-C82W3	HEK293	Biotinylated Cynomolgus / Rhesus macaque FcRn / FCGRT&B2M Heterodimer Protein, His,Avitag™(MALS & SPR verified)
	FCM-C82W5	HEK293	Biotinylated Cynomolgus / Rhesus macaque FcRn Heterodimer Protein, His,Avitag™&Strep II Tag (SPR & BLI verified)
	FCM-P5280	HEK293	Porcine FcRn / FCGRT&B2M Heterodimer Protein, His Tag&Strep II Tag (MALS & SPR verified)
	FCN-F82W3	HEK293	Biotinylated Feline FcRn / FCGRT&B2M Heterodimer Protein, His,Avitag™(MALS & SPR verified)
	FCN-B82W3	HEK293	Biotinylated Bovine FcRn / FCGRT&B2M Heterodimer Protein, His,Avitag™(MALS & SPR verified)

Molecule	Cat. No.	Host	Product Description	Structure
Fc gamma RIIIA / CD16a	CD8-H52H4	HEK293	Human Fc gamma RIIIA / CD16a (V176) Protein, His Tag (SPR & BLI & MALS verified)
	CDA-H5220	HEK293	Human Fc gamma RIIIA / CD16a (F176) Protein, His Tag (SPR & BLI & MALS verified)
	CDA-H5290	HEK293	Human Fc gamma RIIIA / CD16a (V176) Protein, SUMO,His Tag (MALS verified)
	CDA-H52S1	HEK293	Human Fc gamma RIIIA / CD16a (V176) Protein, HSA,His Tag (MALS verified)
	CDA-H82E8	HEK293	Biotinylated Human Fc gamma RIIIA / CD16a (F176) Protein,Avitag™,His Tag (SPR & BLI & MALS verified)
	CDA-H82E9	HEK293	Biotinylated Human Fc gamma RIIIA / CD16a (V176) Protein, Avitag™,His Tag (SPR & BLI verified)
Fc gamma RI / CD64	FCA-H52H1	HEK293	Human Fc gamma RI / CD64 Protein, His Tag (MALS verified)
	FCA-H82E8	HEK293	Biotinylated Human Fc gamma RI / CD64 Protein, His,Avitag™(MALS verified)
	CD4-M5227	HEK293	Mouse Fc gamma RI / CD64 Protein, His Tag (MALS & BLI verified)
	CD4-M82E7	HEK293	Biotinylated Mouse Fc gamma RI / CD64 Protein, His,Avitag™(MALS verified)
	FCA-C82E8	HEK293	Biotinylated Cynomolgus Fc gamma RI / CD64 Protein, His,Avitag™(MALS & BLI verified)
Fc gamma RIIB / CD32b	CDB-M52H7	HEK293	Mouse Fc gamma RIIB / CD32b Protein, His Tag (SPR & BLI & MALS verified)Hot
	CDB-M82E8	HEK293	Biotinylated Mouse Fc gamma RIIB / CD32b Protein,Avitag™,His Tag (SPR & BLI & MALS verified)
	CDB-C5224	HEK293	Cynomolgus Fc gamma RIIB / CD32b Protein, His Tag (MALS & SPR verified)
	CDB-C82E4	HEK293	Biotinylated Cynomolgus Fc gamma RIIB / CD32b Protein, His,Avitag™(SPR & BLI & MALS verified)
Fc gamma RIIB/C / CD32b/c	CDB-H5228	HEK293	Human Fc gamma RIIB/C / CD32b/c Protein, His Tag (SPR & BLI & MALS verified)Hot
	CDB-H5298	HEK293	Human Fc gamma RIIB/C / CD32b/c Protein, SUMO,His Tag (MALS & BLI verified)
	CDB-H52S9	HEK293	Human Fc gamma RIIB/C / CD32b/c Protein, HSA,His Tag (MALS verified)
	CDB-H82E0	HEK293	Biotinylated Human Fc gamma RIIB/C / CD32b/c Protein,Avitag™,His Tag (SPR & BLI & MALS verified)Hot
Fc gamma RIIA / CD32a	CD1-H5223	HEK293	Human Fc gamma RIIA / CD32a (H167) Protein, His Tag (SPR & BLI & MALS verified)Hot
	CDA-H5221	HEK293	Human Fc gamma RIIA / CD32a (R167) Protein, His Tag (MALS & BLI verified)Hot
	CDA-H82E6	HEK293	Biotinylated Human Fc gamma RIIA / CD32a (H167) Protein,Avitag™,His Tag (SPR & BLI & MALS verified)Hot
	CDA-H82E7	HEK293	Biotinylated Human Fc gamma RIIA / CD32a (R167) Protein, Avitag™,His Tag (SPR & BLI & MALS verified)
	CDA-R52H5	HEK293	Rat Fc gamma RIIA / CD32a Protein, His Tag (MALS & SPR verified)
	CDA-C52H7	HEK293	Cynomolgus Fc gamma RIIA / CD32a Protein, His Tag (SPR & BLI & MALS verified)
	CDA-C82E5	HEK293	Biotinylated Cynomolgus Fc gamma RIIA / CD32a Protein, His,Avitag™(SPR & BLI & MALS verified)
	CDA-R52H4	HEK293	Rhesus macaque Fc gamma RIIA / CD32a Protein, His Tag (SPR & BLI & MALS verified)
Fc gamma RIII / CD16	CDA-M52H8	HEK293	Mouse Fc gamma RIII / CD16 Protein, His Tag (SPR & BLI & MALS verified)
	FC6-M82E0	HEK293	Biotinylated Mouse Fc gamma RIII / CD16 Protein, His,Avitag™(MALS verified)
	FC6-C52H9	HEK293	Cynomolgus Fc gamma RIII / CD16 Protein, His Tag (MALS & BLI verified)
	FC6-C82E0	HEK293	Biotinylated Cynomolgus Fc gamma RIII / CD16 Protein, His,Avitag™(MALS & BLI verified)
	FC6-R52H6	HEK293	Rhesus macaque Fc gamma RIII / CD16 Protein, His Tag (SPR & BLI & MALS verified)
Fc gamma RIIIB / CD16b (NA1)	CDB-H5227	HEK293	Human Fc gamma RIIIB / CD16b (NA1) Protein, His Tag (SPR & BLI & MALS verified)
	CDB-H5296	HEK293	Human Fc gamma RIIIB / CD16b (NA1) Protein, SUMO,His Tag (MALS & BLI-verified)
	CDB-H82E4	HEK293	Biotinylated Human Fc gamma RIIIB / CD16b (NA1) Protein, His,Avitag™(SPR & BLI & MALS verified)
Fc gamma RIIIB / CD16b (NA2)	CDB-H5222	HEK293	Human Fc gamma RIIIB / CD16b (NA2) Protein, His Tag (SPR & BLI & MALS verified)
	CDB-H5294	HEK293	Human Fc gamma RIIIB / CD16b (NA2) Protein, SUMO,His Tag (MALS & BLI-verified)
	CDB-H82Ea	HEK293	Biotinylated Human Fc gamma RIIIB / CD16b (NA2) Protein, His,Avitag™(SPR & BLI & MALS verified)
Fc gamma RIV / CD16-2	FC4-M52H3	HEK293	Mouse Fc gamma RIV / CD16-2 Protein, His Tag (MALS verified)
	FC4-M82E8	HEK293	Biotinylated Mouse Fc gamma RIV / CD16-2 Protein, His,Avitag™(BLI verified)

Molecule	Cat. No.	Host	Product Description	Structure
CD23	CD3-H5249	HEK293	Human CD23 / Fc epsilon RII Protein, His Tag (MALS verified)
	CD3-H82Q5	HEK293	Biotinylated Human CD23 / Fc epsilon RII Protein, His,Avitag™(MALS verified)
Fc epsilon RI alpha	FCA-H5228	HEK293	Human Fc epsilon RI alpha Protein, His Tag (MALS verified)
	FCA-H5259	HEK293	Human Fc epsilon RI alpha Protein, Fc Tag (MALS & BLI verified)

References

[1] Randall J Brezski, George Georgiou. Immunoglobulin  isotype knowledge and application to Fc engineering. Current Opinion in  Immunology 2016, 40:62–69.

[2] Derry C. Roopenian, Shreeram Akilesh. FcRn: the  neonatal Fc receptor comes of age. Nature Reviews Immunology. 2007,7:715–725.