1932

Abstract

IgG antibodies mediate a diversity of immune functions by coupling of antigen specificity through the Fab domain to signal transduction via Fc-Fc receptor interactions. Indeed, balanced IgG signaling through type I and type II Fc receptors is required for the control of proinflammatory, anti-inflammatory, and immunomodulatory processes. In this review, we discuss the mechanisms that govern IgG–Fc receptor interactions, highlighting the diversity of Fc receptor–mediated effector functions that regulate immunity and inflammation as well as determine susceptibility to infection and autoimmunity and responsiveness to antibody-based therapeutics and vaccines.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-051116-052433
2017-04-26
2024-04-22
Loading full text...

Full text loading...

/deliver/fulltext/immunol/35/1/annurev-immunol-051116-052433.html?itemId=/content/journals/10.1146/annurev-immunol-051116-052433&mimeType=html&fmt=ahah

Literature Cited

  1. Pincetic A, Bournazos S, DiLillo DJ, Maamary J, Wang TT. 1.  et al. 2014. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat. Immunol. 15:707–16 [Google Scholar]
  2. Nimmerjahn F, Ravetch JV. 2.  2005. Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science 310:1510–12 [Google Scholar]
  3. Sondermann P, Pincetic A, Maamary J, Lammens K, Ravetch JV. 3.  2013. General mechanism for modulating immunoglobulin effector function. PNAS 110:9868–72 [Google Scholar]
  4. Ferrara C, Grau S, Jäger C, Sondermann P, Brünker P. 4.  et al. 2011. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose. PNAS 108:12669–74 [Google Scholar]
  5. de Man YA, Dolhain RJ, Hazes JM. 5.  2014. Disease activity or remission of rheumatoid arthritis before, during and following pregnancy. Curr. Opin. Rheumatol. 26:329–33 [Google Scholar]
  6. Theodoratou E, Thaçi K, Agakov F, Timofeeva MN, Štambuk J. 6.  et al. 2016. Glycosylation of plasma IgG in colorectal cancer prognosis. Sci. Rep. 6:28098 [Google Scholar]
  7. Wang TT, Maamary J, Tan GS, Bournazos S, Davis CW. 7.  et al. 2015. Anti-HA glycoforms drive B cell affinity selection and determine influenza vaccine efficacy. Cell 162:160–69 [Google Scholar]
  8. van de Geijn FE, Wuhrer M, Selman MH, Willemsen SP, de Man YA. 8.  et al. 2009. Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study. Arthritis Res. Ther. 11:R193 [Google Scholar]
  9. Espy C, Morelle W, Kavian N, Grange P, Goulvestre C. 9.  et al. 2011. Sialylation levels of anti-proteinase 3 antibodies are associated with the activity of granulomatosis with polyangiitis (Wegener's). Arthritis Rheum 63:2105–15 [Google Scholar]
  10. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV. 10.  2008. Identification of a receptor required for the anti-inflammatory activity of IVIG. PNAS 105:19571–78 [Google Scholar]
  11. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. 11.  2011. Intravenous gammaglobulin suppresses inflammation through a novel TH2 pathway. Nature 475:110–13 [Google Scholar]
  12. DiLillo DJ, Ravetch JV. 12.  2015. Differential Fc-receptor engagement drives an anti-tumor vaccinal effect. Cell 161:1035–45 [Google Scholar]
  13. Smith P, DiLillo DJ, Bournazos S, Li F, Ravetch JV. 13.  2012. Mouse model recapitulating human Fcγ receptor structural and functional diversity. PNAS 109:6181–86 [Google Scholar]
  14. te Velde AA, de Waal Malefijt R, Huijbens RJ, de Vries JE, Figdor CG. 14.  1992. IL-10 stimulates monocyte FcγR surface expression and cytotoxic activity: distinct regulation of antibody-dependent cellular cytotoxicity by IFN-γ, IL-4, and IL-10. J. Immunol. 149:4048–52 [Google Scholar]
  15. Uciechowski P, Schwarz M, Gessner JE, Schmidt RE, Resch K, Radeke HH. 15.  1998. IFN-γ induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells. Eur. J. Immunol. 28:2928–35 [Google Scholar]
  16. Bournazos S, Ravetch JV. 16.  2015. Fcγ receptor pathways during active and passive immunization. Immunol. Rev. 268:88–103 [Google Scholar]
  17. Kanakaraj P, Duckworth B, Azzoni L, Kamoun M, Cantley LC, Perussia B. 17.  1994. Phosphatidylinositol-3 kinase activation induced upon FcγRIIIA–ligand interaction. J. Exp. Med. 179:551–58 [Google Scholar]
  18. Sánchez-Mejorada G, Rosales C. 18.  1998. Fcγ receptor-mediated mitogen-activated protein kinase activation in monocytes is independent of Ras. J. Biol. Chem. 273:27610–19 [Google Scholar]
  19. Aramburu J, Azzoni L, Rao A, Perussia B. 19.  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. J. Exp. Med. 182:801–10 [Google Scholar]
  20. Nathan C. 20.  2006. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6:173–82 [Google Scholar]
  21. Martyn KD, Kim MJ, Quinn MT, Dinauer MC, Knaus UG. 21.  2005. p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106:3962–69 [Google Scholar]
  22. Suh CI, Stull ND, Li XJ, Tian W, Price MO. 22.  et al. 2006. The phosphoinositide-binding protein p40phox activates the NADPH oxidase during FcγIIA receptor-induced phagocytosis. J. Exp. Med. 203:1915–25 [Google Scholar]
  23. Egesten A, Breton-Gorius J, Guichard J, Gullberg U, Olsson I. 23.  1994. The heterogeneity of azurophil granules in neutrophil promyelocytes: Immunogold localization of myeloperoxidase, cathepsin G, elastase, proteinase 3, and bactericidal/permeability increasing protein. Blood 83:2985–94 [Google Scholar]
  24. Gabay JE, Almeida RP. 24.  1993. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Curr. Opin. Immunol. 5:97–102 [Google Scholar]
  25. Owen CA, Campbell MA, Boukedes SS, Campbell EJ. 25.  1995. Inducible binding of bioactive cathepsin G to the cell surface of neutrophils: a novel mechanism for mediating extracellular catalytic activity of cathepsin G. J. Immunol. 155:5803–10 [Google Scholar]
  26. Odin JA, Edberg JC, Painter CJ, Kimberly RP, Unkeless JC. 26.  1991. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Science 254:1785–88 [Google Scholar]
  27. Sobota A, Strzelecka-Kiliszek A, Gładkowska E, Yoshida K, Mrozińska K, Kwiatkowska K. 27.  2005. Binding of IgG-opsonized particles to FcγR is an active stage of phagocytosis that involves receptor clustering and phosphorylation. J. Immunol. 175:4450–57 [Google Scholar]
  28. Dale DC, Boxer L, Liles WC. 28.  2008. The phagocytes: neutrophils and monocytes. Blood 112:935–45 [Google Scholar]
  29. Selvaraj P, Carpén O, Hibbs ML, Springer TA. 29.  1989. Natural killer cell and granulocyte Fcγ receptor III (CD16) differ in membrane anchor and signal transduction. J. Immunol. 143:3283–88 [Google Scholar]
  30. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L. 30.  et al. 2011. Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49 [Google Scholar]
  31. Clynes R, Ravetch JV. 31.  1995. Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3:21–26 [Google Scholar]
  32. Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV. 32.  1994. FcR γ chain deletion results in pleiotrophic effector cell defects. Cell 76:519–29 [Google Scholar]
  33. Bournazos S, Klein F, Pietzsch J, Seaman MS, Nussenzweig MC, Ravetch JV. 33.  2014. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell 158:1243–53 [Google Scholar]
  34. Bournazos S, Chow SK, Abboud N, Casadevall A, Ravetch JV. 34.  2014. Human IgG Fc domain engineering enhances antitoxin neutralizing antibody activity. J. Clin. Investig. 124:725–29 [Google Scholar]
  35. DiLillo DJ, Tan GS, Palese P, Ravetch JV. 35.  2014. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo. Nat. Med. 20:143–51 [Google Scholar]
  36. Kalergis AM, Ravetch JV. 36.  2002. Inducing tumor immunity through the selective engagement of activating Fcγ receptors on dendritic cells. J. Exp. Med. 195:1653–59 [Google Scholar]
  37. Bournazos S, Woof JM, Hart SP, Dransfield I. 37.  2009. Functional and clinical consequences of Fc receptor polymorphic and copy number variants. Clin. Exp. Immunol. 157:244–54 [Google Scholar]
  38. Karassa FB, Trikalinos TA, Ioannidis JP. 38.  2004. The role of FcγRIIA and IIIA polymorphisms in autoimmune diseases. Biomed. Pharmacother 58286–91 [Google Scholar]
  39. Fanciulli M, Norsworthy PJ, Petretto E, Dong R, Harper L. 39.  et al. 2007. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat. Genet. 39:721–23 [Google Scholar]
  40. Mueller M, Barros P, Witherden AS, Roberts AL, Zhang Z. 40.  et al. 2013. Genomic pathology of SLE-associated copy-number variation at the FCGR2C/FCGR3B/FCGR2B locus. Am. J. Hum. Genet. 92:28–40 [Google Scholar]
  41. Latour S, Fridman WH, Daëron M. 41.  1996. Identification, molecular cloning, biologic properties, and tissue distribution of a novel isoform of murine low-affinity IgG receptor homologous to human FcγRIIB1. J. Immunol. 157:189–97 [Google Scholar]
  42. Amigorena S, Salamero J, Davoust J, Fridman WH, Bonnerot C. 42.  1992. Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG. Nature 358:337–41 [Google Scholar]
  43. Bonnerot C, Briken V, Brachet V, Lankar D, Cassard S. 43.  et al. 1998. syk protein tyrosine kinase regulates Fc receptor γ-chain-mediated transport to lysosomes. EMBO J 17:4606–16 [Google Scholar]
  44. Bergtold A, Desai DD, Gavhane A, Clynes R. 44.  2005. Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity 23:503–14 [Google Scholar]
  45. Swanson JA, Hoppe AD. 45.  2004. The coordination of signaling during Fc receptor-mediated phagocytosis. J. Leukoc. Biol. 76:1093–103 [Google Scholar]
  46. Desai DD, Harbers SO, Flores M, Colonna L, Downie MP. 46.  et al. 2007. Fcγ receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. J. Immunol. 178:6217–26 [Google Scholar]
  47. Clynes RA, Towers TL, Presta LG, Ravetch JV. 47.  2000. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat. Med. 6:443–46 [Google Scholar]
  48. Dhodapkar KM, Kaufman JL, Ehlers M, Banerjee DK, Bonvini E. 48.  et al. 2005. Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells. PNAS 102:2910–15 [Google Scholar]
  49. Bolland S, Yim YS, Tus K, Wakeland EK, Ravetch JV. 49.  2002. Genetic modifiers of systemic lupus erythematosus in FcγRIIB−/− mice. J. Exp. Med. 195:1167–74 [Google Scholar]
  50. Boruchov AM, Heller G, Veri MC, Bonvini E, Ravetch JV, Young JW. 50.  2005. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J. Clin. Investig. 115:2914–23 [Google Scholar]
  51. Gordon S, Plüddemann A, Martinez Estrada F. 51.  2014. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol. Rev. 262:36–55 [Google Scholar]
  52. Clynes R, Maizes JS, Guinamard R, Ono M, Takai T, Ravetch JV. 52.  1999. Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J. Exp. Med. 189:179–85 [Google Scholar]
  53. Dhodapkar KM, Banerjee D, Connolly J, Kukreja A, Matayeva E. 53.  et al. 2007. Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program. J. Exp. Med. 204:1359–69 [Google Scholar]
  54. Yuasa T, Kubo S, Yoshino T, Ujike A, Matsumura K. 54.  et al. 1999. Deletion of Fcγ receptor IIB renders H-2b mice susceptible to collagen-induced arthritis. J. Exp. Med. 189:187–94 [Google Scholar]
  55. Ono M, Okada H, Bolland S, Yanagi S, Kurosaki T, Ravetch JV. 55.  1997. Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 90:293–301 [Google Scholar]
  56. Pearse RN, Kawabe T, Bolland S, Guinamard R, Kurosaki T, Ravetch JV. 56.  1999. SHIP recruitment attenuates FcγRIIB-induced B cell apoptosis. Immunity 10:753–60 [Google Scholar]
  57. Xiang Z, Cutler AJ, Brownlie RJ, Fairfax K, Lawlor KE. 57.  et al. 2007. FcγRIIb controls bone marrow plasma cell persistence and apoptosis. Nat. Immunol. 8:419–29 [Google Scholar]
  58. Ono M, Bolland S, Tempst P, Ravetch JV. 58.  1996. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FcγRIIB. Nature 383:263–66 [Google Scholar]
  59. Bolland S, Ravetch JV. 59.  2000. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 13:277–85 [Google Scholar]
  60. Blank MC, Stefanescu RN, Masuda E, Marti F, King PD. 60.  et al. 2005. Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus. Hum. Genet. 117:220–27 [Google Scholar]
  61. Su K, Wu J, Edberg JC, Li X, Ferguson P. 61.  et al. 2004. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcγRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J. Immunol. 172:7186–91 [Google Scholar]
  62. Floto RA, Clatworthy MR, Heilbronn KR, Rosner DR, MacAry PA. 62.  et al. 2005. Loss of function of a lupus-associated FcγRIIb polymorphism through exclusion from lipid rafts. Nat. Med. 11:1056–58 [Google Scholar]
  63. Henningsson F, Ding Z, Dahlin JS, Linkevicius M, Carlsson F. 63.  et al. 2011. IgE-mediated enhancement of CD4+ T cell responses in mice requires antigen presentation by CD11c+ cells and not by B cells. PLOS ONE 6:e21760 [Google Scholar]
  64. Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV. 64.  1998. Fc receptors are required in passive and active immunity to melanoma. PNAS 95:652–56 [Google Scholar]
  65. Uchida J, Hamaguchi Y, Oliver JA, Ravetch JV, Poe JC. 65.  et al. 2004. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J. Exp. Med. 199:1659–69 [Google Scholar]
  66. Hamaguchi Y, Xiu Y, Komura K, Nimmerjahn F, Tedder TF. 66.  2006. Antibody isotype-specific engagement of Fcγ receptors regulates B lymphocyte depletion during CD20 immunotherapy. J. Exp. Med. 203:743–53 [Google Scholar]
  67. Minard-Colin V, Xiu Y, Poe JC, Horikawa M, Magro CM. 67.  et al. 2008. Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcγRI, FcγRIII, and FcγRIV. Blood 112:1205–13 [Google Scholar]
  68. Biburger M, Aschermann S, Schwab I, Lux A, Albert H. 68.  et al. 2011. Monocyte subsets responsible for immunoglobulin G-dependent effector functions in vivo. Immunity 35:932–44 [Google Scholar]
  69. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P. 69.  et al. 2002. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99:754–58 [Google Scholar]
  70. Weng WK, Levy R. 70.  2003. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J. Clin. Oncol. 21:3940–47 [Google Scholar]
  71. Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M. 71.  et al. 2008. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J. Clin. Oncol. 26:1789–96 [Google Scholar]
  72. Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M. 72.  et al. 2009. Impact of FcγRIIa-FcγRIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J. Clin. Oncol. 27:1122–29 [Google Scholar]
  73. Liu SD, Chalouni C, Young JC, Junttila TT, Sliwkowski MX, Lowe JB. 73.  2015. Afucosylated antibodies increase activation of FcγRIIIa-dependent signaling components to intensify processes promoting ADCC. Cancer Immunol. Res. 3:173–83 [Google Scholar]
  74. Horton HM, Bernett MJ, Pong E, Peipp M, Karki S. 74.  et al. 2008. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res 68:8049–57 [Google Scholar]
  75. Gerdes CA, Nicolini VG, Herter S, van Puijenbroek E, Lang S. 75.  et al. 2013. GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab. Clin. Cancer Res. 19:1126–38 [Google Scholar]
  76. Abes R, Gelize E, Fridman WH, Teillaud JL. 76.  2010. Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood 116:926–34 [Google Scholar]
  77. Hilchey SP, Hyrien O, Mosmann TR, Livingstone AM, Friedberg JW. 77.  et al. 2009. Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab. Blood 113:3809–12 [Google Scholar]
  78. Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. 78.  1992. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N. Engl. J. Med. 327:1209–15 [Google Scholar]
  79. de Bono JS, Rha SY, Stephenson J, Schultes BC, Monroe P. 79.  et al. 2004. Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity. Ann. Oncol. 15:1825–33 [Google Scholar]
  80. Taylor C, Hershman D, Shah N, Suciu-Foca N, Petrylak DP. 80.  et al. 2007. Augmented HER-2–specific immunity during treatment with trastuzumab and chemotherapy. Clin. Cancer Res. 13:5133–43 [Google Scholar]
  81. Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD. 81.  2014. Immune modulation in cancer with antibodies. Annu. Rev. Med. 65:185–202 [Google Scholar]
  82. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD. 82.  et al. 2014. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32:1020–30 [Google Scholar]
  83. Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J. 83.  et al. 2013. Safety and tumor responses with lambrolizumab (anti–PD-1) in melanoma. N. Eng. J. Med. 369:134–44 [Google Scholar]
  84. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA. 84.  et al. 2013. Nivolumab plus ipilimumab in advanced melanoma. N. Eng. J. Med. 369:122–33 [Google Scholar]
  85. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K. 85.  et al. 2013. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J. Exp. Med. 210:1695–710 [Google Scholar]
  86. Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T. 86.  et al. 2013. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol. Res. 1:32–42 [Google Scholar]
  87. Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S. 87.  et al. 2013. Activating Fcγ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J. Exp. Med. 210:1685–93 [Google Scholar]
  88. Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL. 88.  2014. OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy. Immunol. Cell Biol. 92:475–80 [Google Scholar]
  89. Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. 89.  2015. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell 28:285–95 [Google Scholar]
  90. Furness AJ, Vargas FA, Peggs KS, Quezada SA. 90.  2014. Impact of tumour microenvironment and Fc receptors on the activity of immunomodulatory antibodies. Trends Immunol 35:290–98 [Google Scholar]
  91. Romano E, Kusio-Kobialka M, Foukas PG, Baumgaertner P, Meyer C. 91.  et al. 2015. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. PNAS 112:6140–45 [Google Scholar]
  92. Comin-Anduix B, Escuin-Ordinas H, Ibarrondo FJ. 92.  2016. Tremelimumab: research and clinical development. OncoTargets Ther 9:1767–76 [Google Scholar]
  93. Li F, Ravetch JV. 93.  2011. Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333:1030–34 [Google Scholar]
  94. Li F, Ravetch JV. 94.  2012. A general requirement for FcγRIIB co-engagement of agonistic anti-TNFR antibodies. Cell Cycle 11:3343–44 [Google Scholar]
  95. Li F, Ravetch JV. 95.  2012. Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcγ receptor engagement. PNAS 109:10966–71 [Google Scholar]
  96. Li F, Ravetch JV. 96.  2013. Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo. PNAS 110:19501–6 [Google Scholar]
  97. Georgoudaki AM, Prokopec KE, Boura VF, Hellqvist E, Sohn S. 97.  et al. 2016. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep 15:2000–11 [Google Scholar]
  98. French RR, Chan HT, Tutt AL, Glennie MJ. 98.  1999. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat. Med. 5:548–53 [Google Scholar]
  99. Vonderheide RH, Flaherty KT, Khalil M, Stumacher MS, Bajor DL. 99.  et al. 2007. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol. 25:876–83 [Google Scholar]
  100. Ruter J, Antonia SJ, Burris HA, Huhn RD, Vonderheide RH. 100.  2010. Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol. Ther. 10:983–93 [Google Scholar]
  101. Vonderheide RH, Burg JM, Mick R, Trosko JA, Li D. 101.  et al. 2013. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology 2:e23033 [Google Scholar]
  102. Dahan R, Barnhart BC, Li F, Yamniuk AP, Korman AJ, Ravetch JV. 102.  2016. Therapeutic activity of agonistic, human anti-CD40 monoclonal antibodies requires selective FcγR engagement. Cancer Cell 29:820–31 [Google Scholar]
  103. Beppler J, Koehler-Santos P, Pasqualim G, Matte U, Alho CS. 103.  et al. 2016. Fcγ receptor IIA (CD32A) R131 polymorphism as a marker of genetic susceptibility to sepsis. Inflammation 39:518–25 [Google Scholar]
  104. Endeman H, Cornips MC, Grutters JC, van den Bosch JM, Ruven HJ. 104.  et al. 2009. The Fcγ receptor IIA-R/R131 genotype is associated with severe sepsis in community-acquired pneumonia. Clin. Vaccine Immunol. 16:1087–90 [Google Scholar]
  105. Mohsin SN, Mahmood S, Amar A, Ghafoor F, Raza SM, Saleem M. 105.  2015. Association of FcγRIIa polymorphism with clinical outcome of dengue infection: first insight from Pakistan. Am. J. Trop. Med. Hyg 93691–96 [Google Scholar]
  106. Garcia G, Sierra B, Perez AB, Aguirre E, Rosado I. 106.  et al. 2010. Asymptomatic dengue infection in a Cuban population confirms the protective role of the RR variant of the FcγRIIa polymorphism. Am. J. Trop Med. Hyg 821153–56 [Google Scholar]
  107. Okuno Y, Isegawa Y, Sasao F, Ueda S. 107.  1993. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J. Virol. 67:2552–58 [Google Scholar]
  108. Hilleman MR, Werner JH, Gauld RL. 108.  1953. Influenza antibodies in the population of the USA: an epidemiological investigation. Bull. World Health Organ. 8:613–31 [Google Scholar]
  109. Baltimore RS, Kasper DL, Baker CJ, Goroff DK. 109.  1977. Antigenic specificity of opsonophagocytic antibodies in rabbit anti-sera to group B streptococci. J. Immunol. 118:673–78 [Google Scholar]
  110. Townsend AR, Skehel JJ, Taylor PM, Palese P. 110.  1984. Recognition of influenza A virus nucleoprotein by an H-2-restricted cytotoxic T-cell clone. Virology 133:456–59 [Google Scholar]
  111. Knossow M, Gaudier M, Douglas A, Barrère B, Bizebard T. 111.  et al. 2002. Mechanism of neutralization of influenza virus infectivity by antibodies. Virology 302:294–98 [Google Scholar]
  112. Barbey-Martin C, Gigant B, Bizebard T, Calder LJ, Wharton SA. 112.  et al. 2002. An antibody that prevents the hemagglutinin low pH fusogenic transition. Virology 294:70–74 [Google Scholar]
  113. Wang TT, Palese P. 113.  2013. Emergence and evolution of the 1918, 1957, 1968, and 2009 pandemic virus strains. Textbook of Influenza RG Webster, AS Monto, TJ Braciale, RA Lamb 218–30 Chichester, UK: Wiley-Blackwell [Google Scholar]
  114. DiLillo DJ, Palese P, Wilson PC, Ravetch JV. 114.  2016. Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection. J. Clin. Investig. 126:605–10 [Google Scholar]
  115. DiLillo DJ, Tan GS, Palese P, Ravetch JV. 115.  2014. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo. Nat. Med. 20:143–51 [Google Scholar]
  116. Memoli MJ, Shaw PA, Han A, Czajkowski L, Reed S. 116.  et al. 2016. Evaluation of antihemagglutinin and antineuraminidase antibodies as correlates of protection in an influenza A/H1N1 virus healthy human challenge model. mBio 7:e00417–16 [Google Scholar]
  117. Mazor Y, Yang C, Borrok MJ, Ayriss J, Aherne K. 117.  et al. 2016. Enhancement of immune effector functions by modulating IgG's intrinsic affinity for target antigen. PLOS ONE 11:e0157788 [Google Scholar]
  118. Leon PE, He W, Mullarkey CE, Bailey MJ, Miller MS. 118.  et al. 2016. Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact. PNAS 113:E5944–51 [Google Scholar]
  119. Schlessinger J, Steinberg IZ, Givol D, Hochman J, Pecht I. 119.  1975. Antigen-induced conformational changes in antibodies and their Fab fragments studied by circular polarization of fluorescence. PNAS 72:2775–79 [Google Scholar]
  120. Sagawa T, Oda M, Morii H, Takizawa H, Kozono H, Azuma T. 120.  2005. Conformational changes in the antibody constant domains upon hapten-binding. Mol. Immunol. 42:9–18 [Google Scholar]
  121. Eryilmaz E, Janda A, Kim J, Cordero RJ, Cowburn D, Casadevall A. 121.  2013. Global structures of IgG isotypes expressing identical variable regions. Mol. Immunol. 56:588–98 [Google Scholar]
  122. Torres M, Fernandez-Fuentes N, Fiser A, Casadevall A. 122.  2007. The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen. J. Biol. Chem. 282:13917–27 [Google Scholar]
  123. Klein F, Mouquet H, Dosenovic P, Scheid JF, Scharf L, Nussenzweig MC. 123.  2013. Antibodies in HIV-1 vaccine development and therapy. Science 341:1199–204 [Google Scholar]
  124. Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB. 124.  et al. 2000. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 6:207–10 [Google Scholar]
  125. Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ. 125.  et al. 2007. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449:101–4 [Google Scholar]
  126. Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D. 126.  2012. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481:81–84 [Google Scholar]
  127. Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP. 127.  et al. 2015. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 522:487–91 Corrigendum. 2016 Nature 535:580 [Google Scholar]
  128. Lu CL, Murakowski DK, Bournazos S, Schoofs T, Sarkar D. 128.  et al. 2016. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352:1001–4 [Google Scholar]
  129. Halper-Stromberg A, Lu CL, Klein F, Horwitz JA, Bournazos S. 129.  et al. 2014. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 158:989–99 [Google Scholar]
  130. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D. 130.  et al. 2014. Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. PNAS 111:5992–97 [Google Scholar]
  131. Bournazos S, DiLillo DJ, Ravetch JV. 131.  2015. The role of Fc-FcγR interactions in IgG-mediated microbial neutralization. J. Exp. Med. 212:1361–69 [Google Scholar]
  132. Brownlie RJ, Lawlor KE, Niederer HA, Cutler AJ, Xiang Z. 132.  et al. 2008. Distinct cell-specific control of autoimmunity and infection by FcγRIIb. J. Exp. Med. 205:883–95 [Google Scholar]
  133. Clatworthy MR, Smith KG. 133.  2004. FcγRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. J. Exp. Med. 199:717–23 [Google Scholar]
  134. Gonzalez D, Castro OE, Kouri G, Perez J, Martinez E. 134.  et al. 2005. Classical dengue hemorrhagic fever resulting from two dengue infections spaced 20 years or more apart: Havana, Dengue 3 epidemic, 2001–2002. Int. J. Infect. Dis. 9:280–85 [Google Scholar]
  135. Kliks SC, Nimmanitya S, Nisalak A, Burke DS. 135.  1988. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am. J. Trop Med. Hyg 38411–19 [Google Scholar]
  136. Blackley S, Kou Z, Chen H, Quinn M, Rose RC. 136.  et al. 2007. Primary human splenic macrophages, but not T or B cells, are the principal target cells for dengue virus infection in vitro. J. Virol. 81:13325–34 [Google Scholar]
  137. Kou Z, Lim JY, Beltramello M, Quinn M, Chen H. 137.  et al. 2011. Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes. Virology 410:240–47 [Google Scholar]
  138. Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G. 138.  et al. 2016. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with Zika virus. Nat. Immunol. 17:1102–8 [Google Scholar]
  139. Flipse J, Diosa-Toro MA, Hoornweg TE, van de Pol DP, Urcuqui-Inchima S, Smit JM. 139.  2016. Antibody-dependent enhancement of dengue virus infection in primary human macrophages: balancing higher fusion against antiviral responses. Sci. Rep. 6:29201 [Google Scholar]
  140. Modhiran N, Kalayanarooj S, Ubol S. 140.  2010. Subversion of innate defenses by the interplay between DENV and pre-existing enhancing antibodies: TLRs signaling collapse. PLOS Negl. Trop. Dis. 4:e924 [Google Scholar]
  141. Ubol S, Phuklia W, Kalayanarooj S, Modhiran N. 141.  2010. Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. J. Infect. Dis. 201:923–35 [Google Scholar]
  142. Beltramello M, Williams KL, Simmons CP, Macagno A, Simonelli L. 142.  et al. 2010. The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity. Cell Host Microbe 8:271–83 [Google Scholar]
  143. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S. 143.  et al. 2000. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J. Infect. Dis. 181:2–9 [Google Scholar]
  144. Halstead SB, O'Rourke EJ. 144.  1977. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J. Exp. Med. 146:201–17 [Google Scholar]
  145. Moi ML, Takasaki T, Saijo M, Kurane I. 145.  2013. Dengue virus infection-enhancing activity of undiluted sera obtained from patients with secondary dengue virus infection. Trans. R. Soc. Trop. Med. Hyg 10751–58 [Google Scholar]
  146. Guzman MG, Alvarez M, Halstead SB. 146.  2013. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch. Virol. 158:1445–59 [Google Scholar]
  147. Graham BS. 147.  2011. Biological challenges and technological opportunities for respiratory syncytial virus vaccine development. Immunol. Rev. 239:149–66 [Google Scholar]
  148. Monsalvo AC, Batalle JP, Lopez MF, Krause JC, Klemenc J. 148.  et al. 2011. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nat. Med. 17:195–99 [Google Scholar]
  149. Murphy BR, Prince GA, Walsh EE, Kim HW, Parrott RH. 149.  et al. 1986. Dissociation between serum neutralizing and glycoprotein antibody responses of infants and children who received inactivated respiratory syncytial virus vaccine. J. Clin. Microbiol. 24:197–202 [Google Scholar]
  150. Guihot A, Luyt CE, Parrot A, Rousset D, Cavaillon JM. 150.  et al. 2014. Low titers of serum antibodies inhibiting hemagglutination predict fatal fulminant influenza A(H1N1) 2009 infection. Am. J. Respir. Crit. Care Med. 189:1240–49 [Google Scholar]
/content/journals/10.1146/annurev-immunol-051116-052433
Loading
/content/journals/10.1146/annurev-immunol-051116-052433
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error