CD16
| Fc fragment of IgG, low affinity IIIa, receptor (CD16a) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | FCGR3A | ||||||
| Alt. symbols | FCGR3, FCG3 | ||||||
| NCBI gene | 2214 | ||||||
| HGNC | 3619 | ||||||
| OMIM | 146740 | ||||||
| RefSeq | NM_000569 | ||||||
| UniProt | P08637 | ||||||
| Other data | |||||||
| Locus | Chr. 1 q23 | ||||||
| |||||||
| Fc fragment of IgG, low affinity IIIb, receptor (CD16b) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | FCGR3B | ||||||
| Alt. symbols | FCGR3, FCG3 | ||||||
| NCBI gene | 2215 | ||||||
| HGNC | 3620 | ||||||
| OMIM | 610665 | ||||||
| RefSeq | NM_000570 | ||||||
| UniProt | O75015 | ||||||
| Other data | |||||||
| Locus | Chr. 1 q23 | ||||||
| |||||||
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes and macrophages.[1] CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction[2]. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC)[3]. It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.
Function
CD16 is the type III Fcγ receptor. In humans, it exists in two different forms: FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which have 96% sequence similarity in the extracellular immunoglobulin binding regions.[4] While FcγRIIIa is expressed on mast cells, macrophages, and natural killer cells as a transmembrane receptor, FcγRIIIb is only expressed on neutrophils.[4] In addition, FcγRIIIb is the only Fc receptor anchored to the cell membrane by a glycosyl-phosphatidylinositol (GPI) linker, and also plays a significant role in triggering calcium mobilization and neutrophil degranulation. FcγRIIIa and FcγRIIIb together are able to activate degranulation, phagocytosis, and oxidative burst, which allows neutrophils to clear opsonized pathogens.[4]
Mechanism and regulation
These receptors bind to the Fc portion of IgG antibodies, which then activates antibody-dependent cell-mediated cytotoxicity (ADCC) in human NK cells. CD16 is required for ADCC processes carried out by human monocytes.[5] In humans, monocytes expressing CD16 have a variety of ADCC capabilities in the presence of specific antibodies, and can kill primary leukemic cells, cancer cell lines, and cells infected with hepatitis B virus.[5] In addition, CD16 is able to mediate the direct killing of some virally infected and cancer cells without antibodies, playing another role on human NK cells as a lysis receptor.[3]
After binding to ligands such as the conserved section of IgG antibodies, CD16 on human NK cells induce gene transcription of surface activation molecules such as IL-2-R (CD25) and inflammatory cytokines such as IFN-gamma and TNF.[6] This CD16-induced expression of cytokine mRNA in NK cells is mediated by the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of various cytokines. The upregulated expression of specific cytokine genes occurs via a CsA-sensitive and calcium-dependent mechanism.[7]
Structure
The crystal structures of FcεRIα, FcγRIIa, FcγRIIb and FcγRIII have been experimentally determined. These structures revealed a conserved immunoglobulin-like (Ig-like) structure[8]. In addition, the structures demonstrated a common feature in all known Ig superfamily Fc receptors: the acute hinge angle between the N- and C-terminal Ig domains. Specifically, the structure of CD16 (FcγRIIIb) consists of two immunoglobulin-like domains, with an interdomain hinge angle of around 50°[9]. The receptor’s Fc binding region also carries a net positive charge, which complements the negatively-charged receptor binding regions on Fc[9].
As a drug target
Margetuximab targets CD16A in preference to CD16B.[10]
References
- ^ Janeway, Charles (2001). "Appendix II. CD antigens". Immunobiology (5 ed.). New York: Garland. ISBN 0-8153-3642-X.
{{cite book}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - ^ Vivier E, Morin P, O'Brien C, Druker B, Schlossman SF, Anderson P (January 1991). "Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing". Journal of Immunology. 146 (1): 206–10. PMID 1701792.
- ^ a b Mandelboim O, Malik P, Davis DM, Jo CH, Boyson JE, Strominger JL (May 1999). "Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity". Proceedings of the National Academy of Sciences of the United States of America. 96 (10): 5640–4. PMC 21913. PMID 10318937.
- ^ a b c Zhang, Yihong; Boesen, Christian C.; Radaev, Sergei; Brooks, Andrew G.; Fridman, Wolf-Herman; Sautes-Fridman, Catherine; Sun, Peter D. (September 2000). "Crystal Structure of the Extracellular Domain of a Human FcγRIII". Immunity. 13 (3): 387–395. doi:10.1016/S1074-7613(00)00038-8.
{{cite journal}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - ^ a b Yeap WH, Wong KL, Shimasaki N, Teo EC, Quek JK, Yong HX, Diong CP, Bertoletti A, Linn YC, Wong SC (September 2016). "CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes". Scientific Reports. 6 (1): 34310. doi:10.1038/srep34310. PMID 27670158.
- ^ Anegón I, Cuturi MC, Trinchieri G, Perussia B (February 1988). "Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells". The Journal of Experimental Medicine. 167 (2): 452–72. doi:10.1084/jem.167.2.452. PMID 2831292.
- ^ Aramburu J, Azzoni L, Rao A, Perussia B (September 1995). "Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding". The Journal of Experimental Medicine. 182 (3): 801–10. doi:10.1084/jem.182.3.801. PMID 7650486.
- ^ "Crystal Structure of the Human High-Affinity IgE Receptor". Cell. 95 (7): 951–961. 1998-12-23. doi:10.1016/S0092-8674(00)81719-5. ISSN 0092-8674.
- ^ a b "Crystal Structure of the Extracellular Domain of a Human FcγRIII". Immunity. 13 (3): 387–395. 2000-09-01. doi:10.1016/S1074-7613(00)00038-8. ISSN 1074-7613.
- ^ "Margetuximab". AdisInsight. Retrieved 1 February 2017.
External links
- CD16+Antigens at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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