Fc gamma RIII (CD16) Products

Description

Fc gamma receptor III (RIII), also called CD16, is an activating natural killer (NK) cell receptor that binds the Fc portion of immunoglobulin G (IgG) antibodies and is responsible for eliciting a host defense against microbial pathogens (1). Fc gamma RIII (CD16) is one of three subclasses of Fc gamma receptors which includes Fc gamma RI (CD64) and Fc gamma RII (CD32) (1,2). The two forms of Fc gamma RIII are Fc gamma RIIIA (CD16a) and Fc gamma RIIIB (CD16b), which are encoded by two different homologous genes, FCGR3A and FCGR3B, respectively (1-3). The human Fc gamma RIIIA protein is 254 amino acids (aa) in length with a theoretical molecular weight (MW) of 29 kDa, while human Fc gamma RIIIB protein is 233 aa long with a calculated MW of 26 kDa (1,4,5). Each protein contains between five to six glycosylation sites (1,4,5).

Fc gamma RIIIA/CD16a is expressed as a transmembrane protein on NK cells and on a subset of monocytes, macrophages, CD4+T cells, basophils, and mast cells (1-3). Fc gamma RIIIB/CD16b is primarily expressed on neutrophils as a glycosylphosphatidylinositol (GPI)-anchored protein but is also expressed on a subset of basophils and can be induced on eosinophils (1-3). The soluble form of CD16 (sCD16) which is often produced following exposure to inflammatory signals and protein shedding via metalloproteinases (3). Reduced sCD16 levels have been found in patients with multiple myeloma (3).

Activating NK cell receptor function has been harnessed for its potential in tumor immunotherapy (6). One immunotherapy strategy is using bi- and tri-specific NK cell engagers (BiKE and TriKE) to target the Fc gamma RIIIA/CD16a receptor with tumor-associated antigens to stimulate a cytotoxic response and mount an attack on tumor cells (6). CD16a is also capable of antibody dependent cellular cytotoxicity (ADCC) through recognition of antibodies bound to target cells (6-7). CD16-induced NK cell activation allows for NK co-receptor expression including stimulatory receptors like CD137 or inhibitory receptors like TIGIT and PD-1, which serve as additional regulatory checkpoints during ADCC (7). Therapeutic antibodies for cancer treatment like rituximab or trastuzumab can be recognized by Fc gamma RIIIA/CD16a to activate NK cell-mediated killing of tumor cells (6-7).

References

1. Fossati, G., Bucknall, R. C., & Edwards, S. W. (2001). Fcgamma receptors in autoimmune diseases. European Journal of Clinical Investigation, 31(9), 821-831. https://doi.org/10.1046/j.1365-2362.2001.00881.x

2. Patel, K. R., Roberts, J. T., & Barb, A. W. (2019). Multiple Variables at the Leukocyte Cell Surface Impact Fc gamma Receptor-Dependent Mechanisms. Frontiers in Immunology, 10, 223. https://doi.org/10.3389/fimmu.2019.00223

3. Moldovan, I., Galon, J., Maridonneau-Parini, I., Roman Roman, S., Mathiot, C., Fridman, W. H., & Sautes-Fridman, C. (1999). Regulation of production of soluble Fc gamma receptors type III in normal and pathological conditions. Immunology Letters, 68(1), 125-134. https://doi.org/10.1016/s0165-2478(99)00041-3

4. Uniprot (P08637)

5. Uniprot (O75015)

6. Sivori, S., Pende, D., Quatrini, L., Pietra, G., Della Chiesa, M., Vacca, P., Tumino, N., Moretta, F., Mingari, M. C., Locatelli, F., & Moretta, L. (2021). NK cells and ILCs in tumor immunotherapy. Molecular Aspects of Medicine, 80, 100870. https://doi.org/10.1016/j.mam.2020.100870

7. Muntasell, A., Ochoa, M. C., Cordeiro, L., Berraondo, P., Lopez-Diaz de Cerio, A., Cabo, M., Lopez-Botet, M., & Melero, I. (2017). Targeting NK-cell checkpoints for cancer immunotherapy. Current Opinion in Immunology, 45, 73-81. https://doi.org/10.1016/j.coi.2017.01.003

Bioinformatics

Product By Gene ID	2214
Alternate Names	CD16 CD16A Fc fragment of IgG receptor IIIa FCG3 FCGR3 FCGRIII FCR-10 FCRIII FCRIIIA IGFR3 IMD20