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CD16

January 01, 1970

CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells.[1][2] CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction.[3] 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).[4] 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.

Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Identifiers
SymbolFCGR3A
Alt. symbolsFCGR3, FCG3
NCBI gene2214
HGNC3619
OMIM146740
RefSeqNM_000569
UniProtP08637
Other data
LocusChr. 1 q23
Search for
StructuresSwiss-model
DomainsInterPro
Fc fragment of IgG, low affinity IIIb, receptor (CD16b)
Identifiers
SymbolFCGR3B
Alt. symbolsFCGR3, FCG3
NCBI gene2215
HGNC3620
OMIM610665
RefSeqNM_000570
UniProtO75015
Other data
LocusChr. 1 q23
Search for
StructuresSwiss-model
DomainsInterPro

Function edit

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.[5] While FcγRIIIa is expressed on mast cells, macrophages, and natural killer cells as a transmembrane receptor, FcγRIIIb is only expressed on neutrophils.[5] 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.[5]

Mechanism and regulation edit

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.[6] 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.[6] In addition, CD16 is able to mediate the direct killing of some virally infected and cancer cells without antibodies.[4]

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.[7] 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.[8]

Structure edit

The crystal structures of FcεRIα, FcγRIIa, FcγRIIb and FcγRIII have been experimentally determined. These structures revealed a conserved immunoglobulin-like (Ig-like) structure.[9] 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°.[5] The receptor's Fc binding region also carries a net positive charge, which complements the negatively-charged receptor binding regions on Fc.[5]

Clinical significance edit

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.[10] In a normal, healthy individual, cross-linking of CD16 (FcγRIII) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) 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.[10]

CD38 on leukocytes attaching to CD16 on endothelial cells allows for leukocyte binding to blood vessel walls, and the passage of leukocytes through blood vessel walls.[11]

CD16 is often used as an additional marker to reliably identify different subsets of human immune cells.[12] Several other CD molecules, such as CD11b and CD33, are traditionally used as markers for human myeloid-derived suppressor cells (MDSCs).[12] 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.[13] 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.[14]

CD16-positive T cells have been found in patients with chronic viral infections[15][16] or after organ transplantation[17] as well as in patients with severe COVID-19.[2] CD16 expression enables antibody-mediated degranulation and thus allows T cell receptor-independent cytotoxicity. In patients with severe COVID-19, CD16-positive T cells may lead to exacerbated cytotoxicity, promote microvascular endothelial cell injury and contribute to disease severity.[2]

As a drug target edit

With its expression on neutrophils, CD16 represents a possible target in cancer immunotherapy. Margetuximab, an Fc-optimized monoclonal antibody that recognizes the human epidermal growth factor receptor 2 (HER2) expressed on tumor cells in breast, bladder, and other solid tumor cancers, targets CD16A in preference to CD16B.[18] In addition, CD16 could play a role in antibody-targeting cancer therapies. FcγRIV, a murine homologue of CD16A has been shown to be involved in antibody-mediated depletion of tumor-infiltrating regulatory T cells in monoclonal antibody mediated immunotherapy.[19] Bispecific antibody fragments, such as anti-CD19/CD16, allow the targeting of immunotherapeutic drugs to the cancer cell. Anti-CD19/CD16 diabodies have been shown to enhance the natural killer cell response to B-cell lymphomas.[20] Furthermore, targeting extrinsic factors such as FasL or TRAIL to the tumor cell surface triggers death receptors, inducing apoptosis by both autocrine and paracrine processes.

References edit

  1. ^ Janeway C (2001). "Appendix II. CD antigens". Immunobiology (5 ed.). New York: Garland. ISBN 978-0-8153-3642-6.
  2. ^ a b c Georg P, et al. (2021). "Complement activation induces excessive T cell cytotoxicity in severe COVID-19". Cell. 185 (3): 493–512.e25. doi:10.1016/j.cell.2021.12.040. PMC 8712270. PMID 35032429.
  3. ^ 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. doi:10.4049/jimmunol.146.1.206. PMID 1701792.
  4. ^ 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. Bibcode:1999PNAS...96.5640M. doi:10.1073/pnas.96.10.5640. PMC 21913. PMID 10318937.
  5. ^ a b c d e Zhang Y, Boesen CC, Radaev S, Brooks AG, Fridman WH, Sautes-Fridman C, Sun PD (September 2000). "Crystal structure of the extracellular domain of a human FcγRIII". Immunity. 13 (3): 387–95. doi:10.1016/S1074-7613(00)00038-8. PMID 11021536.
  6. ^ 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. Bibcode:2016NatSR...634310Y. doi:10.1038/srep34310. PMC 5037471. PMID 27670158.
  7. ^ 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. PMC 2188858. PMID 2831292.
  8. ^ 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. PMC 2192167. PMID 7650486.
  9. ^ Garman SC, Kinet JP, Jardetzky TS (December 1998). "Crystal structure of the human high-affinity IgE receptor". Cell. 95 (7): 951–61. doi:10.1016/S0092-8674(00)81719-5. PMID 9875849. S2CID 10211658.
  10. ^ a b Goodier MR, Lusa C, Sherratt S, Rodriguez-Galan A, Behrens R, Riley EM (2016). "Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function". Frontiers in Immunology. 7: 384. doi:10.3389/fimmu.2016.00384. PMC 5035824. PMID 27725819.
  11. ^ Quarona V, Zaccarello G, Chillemi A (2013). "CD38 and CD157: a long journey from activation markers to multifunctional molecules". Cytometry Part B. 84 (4): 207–217. doi:10.1002/cyto.b.21092. hdl:2318/134656. PMID 23576305. S2CID 205732787.
  12. ^ a b Pillay J, Tak T, Kamp VM, Koenderman L (October 2013). "Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences". Cellular and Molecular Life Sciences. 70 (20): 3813–27. doi:10.1007/s00018-013-1286-4. PMC 3781313. PMID 23423530.
  13. ^ Dumitru CA, Moses K, Trellakis S, Lang S, Brandau S (August 2012). "Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology". Cancer Immunology, Immunotherapy. 61 (8): 1155–67. doi:10.1007/s00262-012-1294-5. PMC 11028504. PMID 22692756. S2CID 26598520.
  14. ^ Elghetany MT (March 2002). "Surface antigen changes during normal neutrophilic development: a critical review". Blood Cells, Molecules & Diseases. 28 (2): 260–74. doi:10.1006/bcmd.2002.0513. PMID 12064921.
  15. ^ Björkström NK, Gonzalez VD, Malmberg KJ, Falconer K, Alaeus A, Nowak G, Jorns C, Ericzon BG, Weiland O, Sandberg JK, Ljunggren HG (2008). "Elevated numbers of Fc gamma RIIIA+ (CD16+) effector CD8 T cells with NK cell-like function in chronic hepatitis C virus infection". Journal of Immunology. 181 (6): 4219–4228. doi:10.4049/jimmunol.181.6.4219. PMID 18768879. S2CID 7019199.
  16. ^ Clémenceau B, Vivien R, Debeaupuis E, Esbelin J, Biron C, Levy Y, Vié H (2011). "FcγRIIIa (CD16) induction on human T lymphocytes and CD16pos T-lymphocyte amplification". Journal of Immunotherapy. 34 (7): 542–549. doi:10.1097/CJI.0b013e31822801d4. PMID 21760529. S2CID 35442405.
  17. ^ Jacquemont L, Tilly G, Yap M, Doan-Ngoc TM, Danger R, Guérif P, Delbos F, Martinet B, Giral M, Foucher Y, Brouard S, Degauque N (2020). "Terminally Differentiated Effector Memory CD8+ T Cells Identify Kidney Transplant Recipients at High Risk of Graft Failure". Journal of the American Society of Nephrology. 31 (4): 876–891. doi:10.1681/ASN.2019080847. PMC 7191929. PMID 32165419.
  18. ^ "Margetuximab". AdisInsight. Retrieved 1 February 2017.
  19. ^ Sharma N, Vacher J, Allison JP (May 2019). "TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing intratumoral Treg depletion". Proceedings of the National Academy of Sciences of the United States of America. 116 (21): 10453–10462. Bibcode:2019PNAS..11610453S. doi:10.1073/pnas.1819004116. PMC 6534983. PMID 31076558.
  20. ^ Schrama D, Reisfeld RA, Becker JC (February 2006). "Antibody targeted drugs as cancer therapeutics". Nature Reviews. Drug Discovery. 5 (2): 147–59. doi:10.1038/nrd1957. PMID 16424916. S2CID 15164268.

External links edit

January 01, 1970
cd16, also, known, fcγriii, cluster, differentiation, molecule, found, surface, natural, killer, cells, neutrophils, monocytes, macrophages, certain, cells, been, identified, receptors, fcγriiia, fcγriiib, which, participate, signal, transduction, most, well, . CD16 also known as FcgRIII is a cluster of differentiation molecule found on the surface of natural killer cells neutrophils monocytes macrophages and certain T cells 1 2 CD16 has been identified as Fc receptors FcgRIIIa CD16a and FcgRIIIb CD16b which participate in signal transduction 3 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 4 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 Fc fragment of IgG low affinity IIIa receptor CD16a IdentifiersSymbolFCGR3AAlt symbolsFCGR3 FCG3NCBI gene2214HGNC3619OMIM146740RefSeqNM 000569UniProtP08637Other dataLocusChr 1 q23Search forStructuresSwiss modelDomainsInterPro Fc fragment of IgG low affinity IIIb receptor CD16b IdentifiersSymbolFCGR3BAlt symbolsFCGR3 FCG3NCBI gene2215HGNC3620OMIM610665RefSeqNM 000570UniProtO75015Other dataLocusChr 1 q23Search forStructuresSwiss modelDomainsInterPro Contents 1 Function 2 Mechanism and regulation 3 Structure 4 Clinical significance 5 As a drug target 6 References 7 External linksFunction editCD16 is the type III Fcg receptor In humans it exists in two different forms FcgRIIIa CD16a and FcgRIIIb CD16b which have 96 sequence similarity in the extracellular immunoglobulin binding regions 5 While FcgRIIIa is expressed on mast cells macrophages and natural killer cells as a transmembrane receptor FcgRIIIb is only expressed on neutrophils 5 In addition FcgRIIIb 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 FcgRIIIa and FcgRIIIb together are able to activate degranulation phagocytosis and oxidative burst which allows neutrophils to clear opsonized pathogens 5 Mechanism and regulation editThese 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 6 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 6 In addition CD16 is able to mediate the direct killing of some virally infected and cancer cells without antibodies 4 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 7 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 8 Structure editThe crystal structures of FceRIa FcgRIIa FcgRIIb and FcgRIII have been experimentally determined These structures revealed a conserved immunoglobulin like Ig like structure 9 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 FcgRIIIb consists of two immunoglobulin like domains with an interdomain hinge angle of around 50 5 The receptor s Fc binding region also carries a net positive charge which complements the negatively charged receptor binding regions on Fc 5 Clinical significance editCD16 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 10 In a normal healthy individual cross linking of CD16 FcgRIII by immune complexes induces antibody dependent cellular cytotoxicity ADCC 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 10 CD38 on leukocytes attaching to CD16 on endothelial cells allows for leukocyte binding to blood vessel walls and the passage of leukocytes through blood vessel walls 11 CD16 is often used as an additional marker to reliably identify different subsets of human immune cells 12 Several other CD molecules such as CD11b and CD33 are traditionally used as markers for human myeloid derived suppressor cells MDSCs 12 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 13 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 14 CD16 positive T cells have been found in patients with chronic viral infections 15 16 or after organ transplantation 17 as well as in patients with severe COVID 19 2 CD16 expression enables antibody mediated degranulation and thus allows T cell receptor independent cytotoxicity In patients with severe COVID 19 CD16 positive T cells may lead to exacerbated cytotoxicity promote microvascular endothelial cell injury and contribute to disease severity 2 As a drug target editWith its expression on neutrophils CD16 represents a possible target in cancer immunotherapy Margetuximab an Fc optimized monoclonal antibody that recognizes the human epidermal growth factor receptor 2 HER2 expressed on tumor cells in breast bladder and other solid tumor cancers targets CD16A in preference to CD16B 18 In addition CD16 could play a role in antibody targeting cancer therapies FcgRIV a murine homologue of CD16A has been shown to be involved in antibody mediated depletion of tumor infiltrating regulatory T cells in monoclonal antibody mediated immunotherapy 19 Bispecific antibody fragments such as anti CD19 CD16 allow the targeting of immunotherapeutic drugs to the cancer cell Anti CD19 CD16 diabodies have been shown to enhance the natural killer cell response to B cell lymphomas 20 Furthermore targeting extrinsic factors such as FasL or TRAIL to the tumor cell surface triggers death receptors inducing apoptosis by both autocrine and paracrine processes References edit Janeway C 2001 Appendix II CD antigens Immunobiology 5 ed New York Garland ISBN 978 0 8153 3642 6 a b c Georg P et al 2021 Complement activation induces excessive T cell cytotoxicity in severe COVID 19 Cell 185 3 493 512 e25 doi 10 1016 j cell 2021 12 040 PMC 8712270 PMID 35032429 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 doi 10 4049 jimmunol 146 1 206 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 Bibcode 1999PNAS 96 5640M doi 10 1073 pnas 96 10 5640 PMC 21913 PMID 10318937 a b c d e Zhang Y Boesen CC Radaev S Brooks AG Fridman WH Sautes Fridman C Sun PD September 2000 Crystal structure of the extracellular domain of a human FcgRIII Immunity 13 3 387 95 doi 10 1016 S1074 7613 00 00038 8 PMID 11021536 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 Bibcode 2016NatSR 634310Y doi 10 1038 srep34310 PMC 5037471 PMID 27670158 Anegon 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 PMC 2188858 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 PMC 2192167 PMID 7650486 Garman SC Kinet JP Jardetzky TS December 1998 Crystal structure of the human high affinity IgE receptor Cell 95 7 951 61 doi 10 1016 S0092 8674 00 81719 5 PMID 9875849 S2CID 10211658 a b Goodier MR Lusa C Sherratt S Rodriguez Galan A Behrens R Riley EM 2016 Sustained Immune Complex Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function Frontiers in Immunology 7 384 doi 10 3389 fimmu 2016 00384 PMC 5035824 PMID 27725819 Quarona V Zaccarello G Chillemi A 2013 CD38 and CD157 a long journey from activation markers to multifunctional molecules Cytometry Part B 84 4 207 217 doi 10 1002 cyto b 21092 hdl 2318 134656 PMID 23576305 S2CID 205732787 a b Pillay J Tak T Kamp VM Koenderman L October 2013 Immune suppression by neutrophils and granulocytic myeloid derived suppressor cells similarities and differences Cellular and Molecular Life Sciences 70 20 3813 27 doi 10 1007 s00018 013 1286 4 PMC 3781313 PMID 23423530 Dumitru CA Moses K Trellakis S Lang S Brandau S August 2012 Neutrophils and granulocytic myeloid derived suppressor cells immunophenotyping cell biology and clinical relevance in human oncology Cancer Immunology Immunotherapy 61 8 1155 67 doi 10 1007 s00262 012 1294 5 PMC 11028504 PMID 22692756 S2CID 26598520 Elghetany MT March 2002 Surface antigen changes during normal neutrophilic development a critical review Blood Cells Molecules amp Diseases 28 2 260 74 doi 10 1006 bcmd 2002 0513 PMID 12064921 Bjorkstrom NK Gonzalez VD Malmberg KJ Falconer K Alaeus A Nowak G Jorns C Ericzon BG Weiland O Sandberg JK Ljunggren HG 2008 Elevated numbers of Fc gamma RIIIA CD16 effector CD8 T cells with NK cell like function in chronic hepatitis C virus infection Journal of Immunology 181 6 4219 4228 doi 10 4049 jimmunol 181 6 4219 PMID 18768879 S2CID 7019199 Clemenceau B Vivien R Debeaupuis E Esbelin J Biron C Levy Y Vie H 2011 FcgRIIIa CD16 induction on human T lymphocytes and CD16pos T lymphocyte amplification Journal of Immunotherapy 34 7 542 549 doi 10 1097 CJI 0b013e31822801d4 PMID 21760529 S2CID 35442405 Jacquemont L Tilly G Yap M Doan Ngoc TM Danger R Guerif P Delbos F Martinet B Giral M Foucher Y Brouard S Degauque N 2020 Terminally Differentiated Effector Memory CD8 T Cells Identify Kidney Transplant Recipients at High Risk of Graft Failure Journal of the American Society of Nephrology 31 4 876 891 doi 10 1681 ASN 2019080847 PMC 7191929 PMID 32165419 Margetuximab AdisInsight Retrieved 1 February 2017 Sharma N Vacher J Allison JP May 2019 TLR1 2 ligand enhances antitumor efficacy of CTLA 4 blockade by increasing intratumoral Treg depletion Proceedings of the National Academy of Sciences of the United States of America 116 21 10453 10462 Bibcode 2019PNAS 11610453S doi 10 1073 pnas 1819004116 PMC 6534983 PMID 31076558 Schrama D Reisfeld RA Becker JC February 2006 Antibody targeted drugs as cancer therapeutics Nature Reviews Drug Discovery 5 2 147 59 doi 10 1038 nrd1957 PMID 16424916 S2CID 15164268 External links editCD16 Antigens at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title CD16 amp oldid 1221328906, wikipedia, wiki, book, books, library,

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