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CD16 - Revision history
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 22:46, 15 May 2018</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|LocusSupplementaryData=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|LocusSupplementaryData=</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>}}</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>'''CD16''' is a <del style="font-weight: bold; text-decoration: none;">low affinity </del>[[Fc receptor]].</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>'''CD16<ins style="font-weight: bold; text-decoration: none;">,</ins>''' <ins style="font-weight: bold; text-decoration: none;">also known as FcγRIII, </ins>is a [[<ins style="font-weight: bold; text-decoration: none;">cluster of differentiation]] molecule found on the surface of [[natural killer cell]]s, [[neutrophil]] polymorphonuclear leukocytes, [[monocytes]] and [[macrophages]].<ref>{{cite book | last = Janeway | first = Charles | name-list-format = vanc | title = Immunobiology | publisher = Garland | location = New York | year = 2001 | isbn = 0-8153-3642-X | edition = 5 | chapter = Appendix II. CD antigens}}</ref> CD16 has been identified as Fc receptors [[FcγRIIIa]] (CD16a) and [[FcγRIIIb]] (CD16b), which participate in signal transduction.<ref>{{cite journal | vauthors = Vivier E, Morin P, O'Brien C, Druker B, Schlossman SF, Anderson P | title = Tyrosine phosphorylation of the </ins>Fc <ins style="font-weight: bold; text-decoration: none;">gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing | journal = Journal of Immunology | volume = 146 | issue = 1 | pages = 206–10 | date = January 1991 | pmid = 1701792 }}</ref> The most well-researched membrane </ins>receptor <ins style="font-weight: bold; text-decoration: none;">implicated in triggering lysis by NK cells, CD16 is a molecule of the [[immunoglobulin superfamily]] (IgSF) involved in [[Antibody-dependent cell-mediated cytotoxicity|antibody-dependent cellular cytotoxicity]] (ADCC).<ref name="Mandelboim_1999">{{cite journal | vauthors = Mandelboim O, Malik P, Davis DM, Jo CH, Boyson JE, Strominger JL | title = Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 10 | pages = 5640–4 | date = May 1999 | pmid = 10318937 | pmc = 21913 }}</ref> It can be used to isolate populations of specific immune cells through [[fluorescent-activated cell sorting]] (FACS) or [[magnetic-activated cell sorting</ins>]]<ins style="font-weight: bold; text-decoration: none;">, using antibodies directed towards CD16</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">It </del>is <del style="font-weight: bold; text-decoration: none;">a </del>[[<del style="font-weight: bold; text-decoration: none;">cluster of differentiation</del>]] <del style="font-weight: bold; text-decoration: none;">molecule found </del>on <del style="font-weight: bold; text-decoration: none;">the surface of [[</del>natural killer cell<del style="font-weight: bold; text-decoration: none;">]]s</del>, [[<del style="font-weight: bold; text-decoration: none;">neutrophil</del>]] <del style="font-weight: bold; text-decoration: none;">polymorphonuclear leukocytes</del>, [[<del style="font-weight: bold; text-decoration: none;">monocytes</del>]] and [[<del style="font-weight: bold; text-decoration: none;">macrophages</del>]].<ref<del style="font-weight: bold; text-decoration: none;">>{{cite book | last = Janeway | first = Charles | title = Immunobiology | publisher = Garland | location = New York | year = 2001 | isbn = 0-8153-3642-X | edition </del>= <del style="font-weight: bold; text-decoration: none;">5 | chapter = Appendix II. CD antigens}}<</del>/<del style="font-weight: bold; text-decoration: none;">ref</del>> <del style="font-weight: bold; text-decoration: none;">It can be used to isolate populations of these cells by antibodies directed towards CD16, using [[fluorescent-activated cell sorting]] or [[magnetic-activated cell sorting]].</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">== Function ==</ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">CD16 </ins>is <ins style="font-weight: bold; text-decoration: none;">the type III </ins>[[<ins style="font-weight: bold; text-decoration: none;">Neonatal Fc receptor|Fcγ</ins>]] <ins style="font-weight: bold; text-decoration: none;">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.<ref name = "Zhang_2000" /> While FcγRIIIa is expressed </ins>on <ins style="font-weight: bold; text-decoration: none;">mast cells, macrophages, and </ins>natural killer <ins style="font-weight: bold; text-decoration: none;">cells as a transmembrane receptor, FcγRIIIb is only expressed on neutrophils.<ref name="Zhang_2000" /> In addition, FcγRIIIb is the only Fc receptor anchored to the </ins>cell <ins style="font-weight: bold; text-decoration: none;">membrane by a glycosyl-phosphatidylinositol (GPI) linker</ins>, <ins style="font-weight: bold; text-decoration: none;">and also plays a significant role in triggering calcium mobilization and neutrophil </ins>[[<ins style="font-weight: bold; text-decoration: none;">degranulation</ins>]]<ins style="font-weight: bold; text-decoration: none;">. FcγRIIIa and FcγRIIIb together are able to activate degranulation</ins>, [[<ins style="font-weight: bold; text-decoration: none;">phagocytosis</ins>]]<ins style="font-weight: bold; text-decoration: none;">, </ins>and [[<ins style="font-weight: bold; text-decoration: none;">Respiratory burst|oxidative burst</ins>]]<ins style="font-weight: bold; text-decoration: none;">, which allows neutrophils to clear opsonized pathogens</ins>.<ref <ins style="font-weight: bold; text-decoration: none;">name</ins>=<ins style="font-weight: bold; text-decoration: none;">"Zhang_2000" </ins>/></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>==<del style="font-weight: bold; text-decoration: none;">Function</del>==</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>== <ins style="font-weight: bold; text-decoration: none;">Mechanism and regulation </ins>==</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">CD16 has been identified as Fc receptors [[FcγRIIIa]] (CD16a) and [[FcγRIIIb]] (CD16b). </del>These receptors bind to the Fc portion of IgG antibodies which then activates <del style="font-weight: bold; text-decoration: none;">the NK cell for [[</del>antibody-dependent cell-mediated cytotoxicity<del style="font-weight: bold; text-decoration: none;">]]</del>. A <del style="font-weight: bold; text-decoration: none;">lack </del>of CD16 in <del style="font-weight: bold; text-decoration: none;">a given population </del>of <del style="font-weight: bold; text-decoration: none;">neutrophils may indicate prematurity</del>, <del style="font-weight: bold; text-decoration: none;">as could be caused by </del>a [[<del style="font-weight: bold; text-decoration: none;">left shift (medicine)</del>|<del style="font-weight: bold; text-decoration: none;">left shift</del>]] <del style="font-weight: bold; text-decoration: none;">due to neutrophilic leukocytosis induced by tissue necrosis or bacterial infection</del>.<ref>{{cite journal | pmc = <del style="font-weight: bold; text-decoration: none;">4470096 </del>| pmid=<del style="font-weight: bold; text-decoration: none;">26110042 </del>| doi=10.<del style="font-weight: bold; text-decoration: none;">11613</del>/<del style="font-weight: bold; text-decoration: none;">BM</del>.<del style="font-weight: bold; text-decoration: none;">2015</del>.<del style="font-weight: bold; text-decoration: none;">030 </del>| volume=<del style="font-weight: bold; text-decoration: none;">25 </del>| title=<del style="font-weight: bold; text-decoration: none;">Platelet satellitism </del>in <del style="font-weight: bold; text-decoration: none;">infectious disease? </del>| <del style="font-weight: bold; text-decoration: none;">year</del>=<del style="font-weight: bold; text-decoration: none;">2015 </del>| journal=<del style="font-weight: bold; text-decoration: none;">Biochem Med </del>(<del style="font-weight: bold; text-decoration: none;">Zagreb</del>) | pages=<del style="font-weight: bold; text-decoration: none;">285–94 </del>| <del style="font-weight: bold; text-decoration: none;">last1 </del>= <del style="font-weight: bold; text-decoration: none;">Vidranski </del>| <del style="font-weight: bold; text-decoration: none;">first1 </del>= <del style="font-weight: bold; text-decoration: none;">V </del>| <del style="font-weight: bold; text-decoration: none;">last2 </del>= <del style="font-weight: bold; text-decoration: none;">Laskaj </del>| <del style="font-weight: bold; text-decoration: none;">first2 </del>= <del style="font-weight: bold; text-decoration: none;">R </del>| <del style="font-weight: bold; text-decoration: none;">last3 </del>= <del style="font-weight: bold; text-decoration: none;">Sikiric </del>| <del style="font-weight: bold; text-decoration: none;">first3 </del>= <del style="font-weight: bold; text-decoration: none;">D </del>| <del style="font-weight: bold; text-decoration: none;">last4 </del>= <del style="font-weight: bold; text-decoration: none;">Skerk </del>| <del style="font-weight: bold; text-decoration: none;">first4 </del>= <del style="font-weight: bold; text-decoration: none;">V</del>}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>These receptors bind to the Fc portion of IgG antibodies<ins style="font-weight: bold; text-decoration: none;">, </ins>which then activates antibody-dependent cell-mediated cytotoxicity <ins style="font-weight: bold; text-decoration: none;">(ADCC) in human NK cells. CD16 is required for ADCC processes carried out by human monocytes.<ref name="Yeap_2016" /> 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</ins>.<ins style="font-weight: bold; text-decoration: none;"><ref name="Yeap_2016">{{cite journal | vauthors = Yeap WH, Wong KL, Shimasaki N, Teo EC, Quek JK, Yong HX, Diong CP, Bertoletti </ins>A<ins style="font-weight: bold; text-decoration: none;">, Linn YC, Wong SC | title = CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes | language = En | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 34310 | date = September 2016 | pmid = 27670158 | doi = 10.1038/srep34310 }}</ref> In addition, CD16 is able to mediate the direct killing of some virally infected and cancer cells without antibodies.<ref name="Mandelboim_1999" /></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">After binding to ligands such as the conserved section of IgG antibodies, CD16 on human NK cells induce gene transcription </ins>of <ins style="font-weight: bold; text-decoration: none;">surface activation molecules such as IL-2-R (CD25) and inflammatory cytokines such as IFN-gamma and TNF.<ref>{{cite journal | vauthors = Anegón I, Cuturi MC, Trinchieri G, Perussia B | title = 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 = The Journal of Experimental Medicine | volume = 167 | issue = 2 | pages = 452–72 | date = February 1988 | pmid = 2831292 | doi = 10.1084/jem.167.2.452 | url = http://jem.rupress.org/content/167/2/452 }}</ref> This </ins>CD16<ins style="font-weight: bold; text-decoration: none;">-induced expression of cytokine mRNA </ins>in <ins style="font-weight: bold; text-decoration: none;">NK cells is mediated by the nuclear factor </ins>of <ins style="font-weight: bold; text-decoration: none;">activated T cells (NFATp)</ins>, a [[<ins style="font-weight: bold; text-decoration: none;">Ciclosporin</ins>|<ins style="font-weight: bold; text-decoration: none;">cyclosporin A</ins>]] <ins style="font-weight: bold; text-decoration: none;">(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</ins>.<ref>{{cite journal <ins style="font-weight: bold; text-decoration: none;">| vauthors = Aramburu J, Azzoni L, Rao A, Perussia B | title = 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 = The Journal of Experimental Medicine | volume = 182 | issue = 3 | pages = 801–10 | date = September 1995 | pmid = 7650486 | doi = 10.1084/jem.182.3.801 | url = http://jem.rupress.org/content/182/3/801 </ins>| pmc = <ins style="font-weight: bold; text-decoration: none;">2192167 }}</ref></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">== Structure ==</ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">The crystal structures of FcεRIα, FcγRIIa, FcγRIIb and FcγRIII have been experimentally determined. These structures revealed a conserved immunoglobulin-like (Ig-like) structure.<ref name="Garman_1998">{{cite journal | vauthors = Garman SC, Kinet JP, Jardetzky TS | title = Crystal structure of the human high-affinity IgE receptor | journal = Cell | volume = 95 | issue = 7 | pages = 951–61 | date = December 1998 </ins>| pmid = <ins style="font-weight: bold; text-decoration: none;">9875849 </ins>| doi = 10.<ins style="font-weight: bold; text-decoration: none;">1016</ins>/<ins style="font-weight: bold; text-decoration: none;">S0092-8674(00)81719-5 }}</ref> 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</ins>. <ins style="font-weight: bold; text-decoration: none;">Specifically, the structure of CD16 (FcγRIIIb) consists of two immunoglobulin-like domains, with an interdomain hinge angle of around 50°</ins>.<ins style="font-weight: bold; text-decoration: none;"><ref name="Zhang_2000">{{cite journal | vauthors = Zhang Y, Boesen CC, Radaev S, Brooks AG, Fridman WH, Sautes-Fridman C, Sun PD | title = Crystal structure of the extracellular domain of a human FcγRIII | journal = Immunity </ins>| volume = <ins style="font-weight: bold; text-decoration: none;">13 | issue = 3 | pages = 387–95 | date = September 2000 | pmid = 11021536 | doi = 10.1016/S1074-7613(00)00038-8 }}</ref> The receptor’s Fc binding region also carries a net positive charge, which complements the negatively-charged receptor binding regions on Fc.<ref name="Zhang_2000" /></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">== Clinical significance ==</ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">CD16 plays a significant role in early activation of natural killer (NK) cells following vaccination. In addition, CD16 downregulation represents a possible way to moderate NK cell responses and maintain immune homeostasis in both T cell and antibody-dependent signaling pathways.<ref name="Goodier_2016">{{cite journal | vauthors = Goodier MR, Lusa C, Sherratt S, Rodriguez-Galan A, Behrens R, Riley EM </ins>| title = <ins style="font-weight: bold; text-decoration: none;">Sustained Immune Complex-Mediated Reduction </ins>in <ins style="font-weight: bold; text-decoration: none;">CD16 Expression after Vaccination Regulates NK Cell Function </ins>| <ins style="font-weight: bold; text-decoration: none;">language </ins>= <ins style="font-weight: bold; text-decoration: none;">English </ins>| journal = <ins style="font-weight: bold; text-decoration: none;">Frontiers in Immunology | volume = 7 | pages = 384 | date = 2016 | pmid = 27725819 | doi = 10.3389/fimmu.2016.00384 | url = https://www.frontiersin.org/articles/10.3389/fimmu.2016.00384/full }}</ref> In a normal, healthy individual, cross-linking of CD16 (FcγRIII) by immune complexes induces antibody-dependent cellular cytotoxicity </ins>(<ins style="font-weight: bold; text-decoration: none;">ADCC</ins>) <ins style="font-weight: bold; text-decoration: none;">in NK cells. However, this pathway can also be targeted in cancerous or diseased cells by immunotherapy. After influenza vaccination, CD16 downregulation was associated with significant upregulation of influenza-specific plasma antibodies, and positively correlated with degranulation of NK cells.<ref name="Goodier_2016" /></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">CD16 is often used as an additional marker to reliably identify different subsets of human immune cells.<ref name="Pillay_2013">{{cite journal | vauthors = Pillay J, Tak T, Kamp VM, Koenderman L | title = Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences | journal = Cellular and Molecular Life Sciences | volume = 70 | issue = 20 </ins>| pages = <ins style="font-weight: bold; text-decoration: none;">3813–27 </ins>| <ins style="font-weight: bold; text-decoration: none;">date </ins>= <ins style="font-weight: bold; text-decoration: none;">October 2013 </ins>| <ins style="font-weight: bold; text-decoration: none;">pmid </ins>= <ins style="font-weight: bold; text-decoration: none;">23423530 </ins>| <ins style="font-weight: bold; text-decoration: none;">pmc </ins>= <ins style="font-weight: bold; text-decoration: none;">3781313 </ins>| <ins style="font-weight: bold; text-decoration: none;">doi </ins>= <ins style="font-weight: bold; text-decoration: none;">10.1007/s00018-013-1286-4 }}</ref> Several other CD molecules, such as CD11b and CD33, are traditionally used as markers for human myeloid-derived suppressor cells (MDSCs).<ref name="Pillay_2013" /> However, since these markers are also expressed on NK cells and all other cells derived from myelocytes, other markers are required, such as CD14 and CD15. Neutrophils are found to be CD14low and CD15high, whereas monocytes are CD14high and CD15low.<ref>{{cite journal | vauthors = Dumitru CA, Moses K, Trellakis S, Lang S, Brandau S | title = Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology | journal = Cancer Immunology, Immunotherapy | volume = 61 | issue = 8 | pages = 1155–67 | date = August 2012 | pmid = 22692756 | doi = 10.1007/s00262-012-1294-5 }}</ref> While these two markers are sufficient to differentiate between neutrophils and monocytes, eosinophils have a similar CD15 expression to neutrophils. Therefore, CD16 is used as a further marker to identify neutrophils: mature neutrophils are CD16high, while eosinophils and monocytes are both CD16low. CD16 allows for distinction between these two types of granulocytes. Additionally, CD16 expression varies between the different stages of neutrophil development: neutrophil progenitors that have differentiation capacity are CD16low, with increasing expression of CD16 in metamyelocytes, banded, and mature neutrophils, respectively.<ref>{{cite journal | vauthors = Elghetany MT | title = Surface antigen changes during normal neutrophilic development: a critical review | journal = Blood Cells, Molecules & Diseases | volume = 28 </ins>| <ins style="font-weight: bold; text-decoration: none;">issue </ins>= <ins style="font-weight: bold; text-decoration: none;">2 </ins>| <ins style="font-weight: bold; text-decoration: none;">pages </ins>= <ins style="font-weight: bold; text-decoration: none;">260–74 </ins>| <ins style="font-weight: bold; text-decoration: none;">date </ins>= <ins style="font-weight: bold; text-decoration: none;">March 2002 </ins>| <ins style="font-weight: bold; text-decoration: none;">pmid </ins>= <ins style="font-weight: bold; text-decoration: none;">12064921 </ins>}}</ref></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==As a drug target==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==As a drug target==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[Margetuximab]] targets CD16A in preference to CD16B.<ref>{{cite web|title=Margetuximab|url=http://adisinsight.springer.com/drugs/800022516|website=AdisInsight|<del style="font-weight: bold; text-decoration: none;">accessdate</del>=1 February 2017}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">With its expression on neutrophils, CD16 represents a possible target in cancer immunotherapy. </ins>[[Margetuximab]]<ins style="font-weight: bold; text-decoration: none;">, an Fc-optimized monoclonal antibody that recognizes the [[HER2/neu|human epidermal growth factor receptor 2 (HER2)]] expressed on tumor cells in breast, bladder, and other solid tumor cancers, </ins>targets CD16A in preference to CD16B.<ref>{{cite web | title = Margetuximab | url = http://adisinsight.springer.com/drugs/800022516 | website = AdisInsight | <ins style="font-weight: bold; text-decoration: none;">access-date </ins>= 1 February 2017 }}</ref> <ins style="font-weight: bold; text-decoration: none;">In addition, CD16 could play a role in antibody-targeting cancer therapies. Bispecific antibody fragments, such as anti-[[CD19]]/CD16, allow the targeting of immunotherapeutic drugs to the cancer cell. Anti-CD19/CD16 [[Single-chain variable fragment|diabodies]] have been shown to enhance the natural killer cell response to B-cell [[Lymphoma|lymphomas]].<ref>{{cite journal | vauthors = Schrama D, Reisfeld RA, Becker JC | title = Antibody targeted drugs as cancer therapeutics | journal = Nature Reviews. Drug Discovery | volume = 5 | issue = 2 | pages = 147-59 | date = February 2006 | pmid = 16424916 | doi = 10.1038/nrd1957 }}</ref> Furthermore, targeting extrinsic factors such as [[Fas ligand|FasL]] or [[TRAIL]] to the tumor cell surface triggers death receptors, inducing apoptosis by both autocrine and paracrine processes.</ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>==References==</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>== References ==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>{{Reflist}}</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>{{Reflist<ins style="font-weight: bold; text-decoration: none;">|32em</ins>}}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>==External links==</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>== External links ==</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>* {{MeshName|CD16+Antigens}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>* {{MeshName|CD16+Antigens}}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
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<td colspan="2" class="diff-lineno">Line 72:</td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Fc receptors]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Fc receptors]]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"></del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"></del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">{{gene-1-stub}}</del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">{{immunology-stub}}</del></div></td><td colspan="2" class="diff-side-added"></td></tr>
</table>
imported>OAbot
https://www.wikidoc.org/index.php?title=CD16&diff=1410577&oldid=prev
en>Rod57: /* Function */ ==As a drug target== Margetuximab targets CD16A in preference to CD16B.<ref
2017-02-27T16:12:38Z
<p><span dir="auto"><span class="autocomment">Function: </span> ==As a drug target== <a href="/index.php?title=Margetuximab&action=edit&redlink=1" class="new" title="Margetuximab (page does not exist)">Margetuximab</a> targets CD16A in preference to CD16B.<ref</span></p>
<p><b>New page</b></p><div>{{infobox protein<br />
|Name= [[FCGR3A|Fc fragment of IgG, low affinity IIIa, receptor (CD16a)]]<br />
|caption=<br />
|image=<br />
|width=<br />
|HGNCid=3619<br />
|Symbol=[[FCGR3A]]<br />
|AltSymbols=FCGR3, FCG3<br />
|EntrezGene=2214<br />
|OMIM=146740<br />
|RefSeq=NM_000569<br />
|UniProt=P08637<br />
|PDB=<br />
|ECnumber=<br />
|Chromosome=1<br />
|Arm=q<br />
|Band=23<br />
|LocusSupplementaryData=<br />
}}<br />
{{infobox protein<br />
|Name=[[FCGR3B|Fc fragment of IgG, low affinity IIIb, receptor (CD16b)]]<br />
|caption=<br />
|image=<br />
|width=<br />
|HGNCid=3620<br />
|Symbol=[[FCGR3B]]<br />
|AltSymbols=FCGR3, FCG3<br />
|EntrezGene=2215<br />
|OMIM=610665<br />
|RefSeq=NM_000570<br />
|UniProt=O75015<br />
|PDB=<br />
|ECnumber=<br />
|Chromosome=1<br />
|Arm=q<br />
|Band=23<br />
|LocusSupplementaryData=<br />
}}<br />
'''CD16''' is a low affinity [[Fc receptor]].<br />
<br />
It is a [[cluster of differentiation]] molecule found on the surface of [[natural killer cell]]s, [[neutrophil]] polymorphonuclear leukocytes, [[monocytes]] and [[macrophages]].<ref>{{cite book | last = Janeway | first = Charles | title = Immunobiology | publisher = Garland | location = New York | year = 2001 | isbn = 0-8153-3642-X | edition = 5 | chapter = Appendix II. CD antigens}}</ref> It can be used to isolate populations of these cells by antibodies directed towards CD16, using [[fluorescent-activated cell sorting]] or [[magnetic-activated cell sorting]].<br />
<br />
==Function==<br />
<br />
CD16 has been identified as Fc receptors [[FcγRIIIa]] (CD16a) and [[FcγRIIIb]] (CD16b). These receptors bind to the Fc portion of IgG antibodies which then activates the NK cell for [[antibody-dependent cell-mediated cytotoxicity]]. A lack of CD16 in a given population of neutrophils may indicate prematurity, as could be caused by a [[left shift (medicine)|left shift]] due to neutrophilic leukocytosis induced by tissue necrosis or bacterial infection.<ref>{{cite journal | pmc = 4470096 | pmid=26110042 | doi=10.11613/BM.2015.030 | volume=25 | title=Platelet satellitism in infectious disease? | year=2015 | journal=Biochem Med (Zagreb) | pages=285–94 | last1 = Vidranski | first1 = V | last2 = Laskaj | first2 = R | last3 = Sikiric | first3 = D | last4 = Skerk | first4 = V}}</ref><br />
<br />
==As a drug target==<br />
[[Margetuximab]] targets CD16A in preference to CD16B.<ref>{{cite web|title=Margetuximab|url=http://adisinsight.springer.com/drugs/800022516|website=AdisInsight|accessdate=1 February 2017}}</ref><br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
==External links==<br />
* {{MeshName|CD16+Antigens}}<br />
<br />
{{Clusters of differentiation}}<br />
{{Clusters of differentiation by lineage}}<br />
{{Immune receptors}}<br />
<br />
{{DEFAULTSORT:Cd16}}<br />
[[Category:Clusters of differentiation]]<br />
[[Category:Fc receptors]]<br />
<br />
<br />
{{gene-1-stub}}<br />
{{immunology-stub}}</div>
en>Rod57