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 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.[4] 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.[4] 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.[5] 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.[6]
A lack of CD16 in a given population of neutrophils may indicate prematurity, as could be caused by a left shift due to neutrophilic leukocytosis induced by tissue necrosis or bacterial infection.[7]
As a drug target
Margetuximab targets CD16A in preference to CD16B.[8]
References
- ^ Janeway, Charles (2001). "Appendix II. CD antigens". Immunobiology (5 ed.). New York: Garland. ISBN 0-8153-3642-X.
- ^ Vivier, E.; Morin, P.; O'Brien, C.; Druker, B.; Schlossman, S. F.; Anderson, P. (1991-01-01). "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 (Baltimore, Md.: 1950). 146 (1): 206–210. ISSN 0022-1767. PMID 1701792.
- ^ a b Mandelboim, Ofer; Malik, Pratap; Davis, Daniel M.; Jo, Chang H.; Boyson, Jonathan E.; Strominger, Jack L. (1999-05-11). "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): 5640–5644. ISSN 0027-8424. PMID 10318937.
- ^ 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, M. C.; Trinchieri, G.; Perussia, B. (1988-02-01). "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". Journal of Experimental Medicine. 167 (2): 452–472. doi:10.1084/jem.167.2.452. ISSN 0022-1007. PMID 2831292.
- ^ Aramburu, J.; Azzoni, L.; Rao, A.; Perussia, B. (1995-09-01). "Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding". Journal of Experimental Medicine. 182 (3): 801–810. doi:10.1084/jem.182.3.801. ISSN 0022-1007. PMID 7650486.
- ^ Vidranski V, Laskaj R, Sikiric D, Skerk V (2015). "Platelet satellitism in infectious disease?". Biochemia Medica. 25 (2): 285–94. doi:10.11613/BM.2015.030. PMC 4470096. PMID 26110042.
- ^ "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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