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Cross-presentation of IgG-containing immune complexes

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Abstract

IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4+ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8+ T cells.

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References

  1. Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140(6):805–820

    Article  PubMed  CAS  Google Scholar 

  2. Cerutti A, Puga I, Cols M (2011) Innate control of B cell responses. Trends Immunol 32(5):202–211

    Article  PubMed  CAS  Google Scholar 

  3. He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, Shan M, Chadburn A, Villanacci V, Plebani A, Knowles DM, Rescigno M, Cerutti A (2007) Intestinal bacteria trigger T cell-independent immunoglobulin A2 class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26(6):812–826

    Article  PubMed  CAS  Google Scholar 

  4. Casadevall A, Pirofski LA (2003) Antibody-mediated regulation of cellular immunity and the inflammatory response. Trends Immunol 24(9):474–478

    Article  PubMed  CAS  Google Scholar 

  5. Rodewald R, Kraehenbuhl JP (1984) Receptor-mediated transport of IgG. J Cell Biol 99(1):159s–164s

    Article  PubMed  CAS  Google Scholar 

  6. Mi W, Wanjie S, Lo ST, Gan Z, Pickl-Herk B, Ober RJ, Ward ES (2008) Targeting the neonatal fc receptor for antigen delivery using engineered fc fragments. J Immunol 181(11):7550–7561

    PubMed  CAS  Google Scholar 

  7. Ober RJ, Martinez C, Lai X, Zhou J, Ward ES (2004) Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at the single-molecule level. Proc Natl Acad Sci USA 101(30):11076–11081

    Article  PubMed  CAS  Google Scholar 

  8. Ober RJ, Martinez C, Vaccaro C, Zhou J, Ward ES (2004) Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor. FcRn. J Immunol 172(4):2021–2029

    CAS  Google Scholar 

  9. Qiao SW, Kobayashi K, Johansen FE, Sollid LM, Andersen JT, Milford E, Roopenian DC, Lencer WI, Blumberg RS (2008) Dependence of antibody-mediated presentation of antigen on FcRn. Proc Natl Acad Sci USA 105(27):9337–9342

    Article  PubMed  CAS  Google Scholar 

  10. Akilesh S, Christianson GJ, Roopenian DC, Shaw AS (2007) Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol 179(7):4580–4588

    PubMed  CAS  Google Scholar 

  11. Amigorena S, Lankar D, Briken V, Gapin L, Viguier M, Bonnerot C (1998) Type II and III receptors for immunoglobulin G (IgG) control the presentation of different T cell epitopes from single IgG-complexed antigens. J Exp Med 187(4):505–515

    Article  PubMed  CAS  Google Scholar 

  12. Simitsek PD, Campbell DG, Lanzavecchia A, Fairweather N, Watts C (1995) Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants. J Exp Med 181(6):1957–1963

    Article  PubMed  CAS  Google Scholar 

  13. Barrington RA, Pozdnyakova O, Zafari MR, Benjamin CD, Carroll MC (2002) B lymphocyte memory. J Exp Med 196(9):1189–1200

    Article  PubMed  CAS  Google Scholar 

  14. Liu W, Meckel T, Tolar P, Sohn HW, Pierce SK (2010) Antigen affinity discrimination is an intrinsic function of the B cell receptor. J Exp Med 207(5):1095–1111

    Article  PubMed  CAS  Google Scholar 

  15. Macardle PJ, Mardell C, Bailey S, Wheatland L, Ho A, Jessup C, Roberton DM, Zola H (2002) FcγRIIb expression on human germinal center B lymphocytes. Eur J Immunol 32(12):3736–3744

    Article  PubMed  CAS  Google Scholar 

  16. Bevan MJ (1976) Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med 143(5):1283–1288

    Article  PubMed  CAS  Google Scholar 

  17. Bevan MJ (1976) Minor H antigens introduced on H-2 different stimulating cells cross-react at the cytotoxic T cell level during in vivo priming. J Immunol 117(6):2233–2238

    PubMed  CAS  Google Scholar 

  18. Rock KL, Gamble S, Rothstein L (1990) Presentation of exogenous antigen with class I major histocompatibility complex molecules. Science 249(4971):918–921

    Article  PubMed  CAS  Google Scholar 

  19. Kreer C, Rauen J, Zehner M, Burgdorf S (2012) Cross-presentation: how to get there—or how to get the ER. Front Immunol 2:87. doi:10.3389/fimmu.2011.00087

    Article  Google Scholar 

  20. Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A (2011) CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proc Natl Acad Sci USA 108(21):8749–8754

    Article  PubMed  CAS  Google Scholar 

  21. Shedlock DJ, Shen H (2003) Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300(5617):337

    Article  PubMed  CAS  Google Scholar 

  22. Reiser M, Wieland A, Plachter B, Mertens T, Greiner J, Schirmbeck R (2011) The immunodominant CD8 T cell response to the human cytomegalovirus tegument phosphoprotein pp 65(495–503) epitope critically depends on CD4 T cell help in vaccinated HLA-A*0201 transgenic mice. J Immunol 187(5):2172–2180

    Article  PubMed  CAS  Google Scholar 

  23. Ackerman AL, Cresswell P (2004) Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 5(7):678–684

    Article  PubMed  CAS  Google Scholar 

  24. Amigorena S, Savina A (2010) Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol 22(1):109–117

    Article  PubMed  CAS  Google Scholar 

  25. Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, Huang Y, Rodriguez A, Clausen BE, Park CG, Trumpfheller C, Steinman RM (2011) Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci USA 108(6):2384–2389

    Article  PubMed  CAS  Google Scholar 

  26. Bozzacco L, Trumpfheller C, Siegal FP, Mehandru S, Markowitz M, Carrington M, Nussenzweig MC, Piperno AG, Steinman RM (2007) DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes. Proc Natl Acad Sci USA 104(4):1289–1294

    Article  PubMed  CAS  Google Scholar 

  27. Cheong C, Choi J-H, Vitale L, He L-Z, Trumpfheller C, Bozzacco L, Do Y, Nchinda G, Park SH, Dandamudi DB, Shrestha E, Pack M, Lee H-W, Keler T, Steinman RM, Park CG (2010) Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116(19):3828–3838

    Article  PubMed  CAS  Google Scholar 

  28. Baker K, Qiao S-W, Kuo TT, Aveson VG, Platzer B, Andersen J-T, Sandlie I, Chen Z, de Haar C, Lencer WI, Fiebiger E, Blumberg RS (2011) Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8−CD11b+dendritic cells. Proc Natl Acad Sci USA 108(24):9927–9932

    Article  PubMed  CAS  Google Scholar 

  29. Amigorena S, Bonnerot C (1999) Fc receptors for IgG and antigen presentation on MHC class I and class II molecules. Semin Immunol 11(6):385–390

    Article  PubMed  CAS  Google Scholar 

  30. Segura E, Villadangos JA (2009) Antigen presentation by dendritic cells in vivo. Curr Opin Immunol 21(1):105–110

    Article  PubMed  CAS  Google Scholar 

  31. Villadangos JA, Schnorrer P (2007) Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol 7(7):543–555

    Article  PubMed  CAS  Google Scholar 

  32. Pulendran B, Tang H, Denning TL (2008) Division of labor, plasticity, and crosstalk between dendritic cell subsets. Curr Opin Immunol 20(1):61–67

    Article  PubMed  CAS  Google Scholar 

  33. Kelsall BL, Leon F (2005) Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease. Immunol Rev 206:132–148

    Article  PubMed  CAS  Google Scholar 

  34. Kelsall B (2008) Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages. Mucosal Immunol 1(6):460–469

    Article  PubMed  CAS  Google Scholar 

  35. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, Luche H, Fehling HJ, Hardt W-D, Shakhar G, Jung S (2009) Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31(3):502–512

    Article  PubMed  CAS  Google Scholar 

  36. Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B, Margalit R, Kalchenko V, Geissmann F, Jung S (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204(1):171–180

    Article  PubMed  CAS  Google Scholar 

  37. Heath WR, Carbone FR (2009) Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat Immunol 10(12):1237–1244

    Article  PubMed  CAS  Google Scholar 

  38. Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322(5904):1097–1100

    Article  PubMed  CAS  Google Scholar 

  39. Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen C-JJ, Dunbar PR, Wadley RB, Jeet V, Vulink AJE, Hart DNJ, Radford KJ (2010) Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med 207(6):1247–1260

    Article  PubMed  CAS  Google Scholar 

  40. Kamphorst AO, Guermonprez P, Dudziak D, Nussenzweig MC (2010) Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes. J Immunol 185(6):3426–3435

    Article  PubMed  CAS  Google Scholar 

  41. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee H-W, Park CG, Steinman RM, Nussenzweig MC (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315(5808):107–111

    Article  PubMed  CAS  Google Scholar 

  42. Schnorrer P, Behrens GM, Wilson NS, Pooley JL, Smith CM, El-Sukkari D, Davey G, Kupresanin F, Li M, Maraskovsky E, Belz GT, Carbone FR, Shortman K, Heath WR, Villadangos JA (2006) The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture. Proc Natl Acad Sci USA 103(28):10729–10734

    Article  PubMed  CAS  Google Scholar 

  43. Savina A, Jancic C, Hugues S, Guermonprez P, Vargas P, Moura IC, Lennon-Duménil A-M, Seabra MC, Raposo G, Amigorena S (2006) NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126(1):205–218

    Article  PubMed  CAS  Google Scholar 

  44. Jancic C, Savina A, Wasmeier C, Tolmachova T, El-Benna J, Dang PM-C, Pascolo S, Gougerot-Pocidalo M-A, Raposo G, Seabra MC, Amigorena S (2007) Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes. Nat Cell Biol 9(4):367–378

    Article  PubMed  CAS  Google Scholar 

  45. Jusforgues-Saklani H, Uhl M, Blachere N, Lemaitre F, Lantz O, Bousso P, Braun D, Moon JJ, Albert ML (2008) Antigen persistence is required for dendritic cell licensing and CD8+ T cell cross-priming. J Immunol 181(5):3067–3076

    PubMed  CAS  Google Scholar 

  46. Savina A, Amigorena S (2007) Phagocytosis and antigen presentation in dendritic cells. Immunol Rev 219(1):143–156

    Article  PubMed  CAS  Google Scholar 

  47. Russell DG (2007) New ways to arrest phagosome maturation. Nat Cell Biol 9(4):357–359

    Article  PubMed  CAS  Google Scholar 

  48. Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I (2003) Activation of lysosomal function during dendritic cell maturation. Science 299(5611):1400–1403

    Article  PubMed  CAS  Google Scholar 

  49. Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES (2005) Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307(5715):1630–1634

    Article  PubMed  CAS  Google Scholar 

  50. Cebrian I, Visentin G, Blanchard N, Jouve M, Bobard A, Moita C, Enninga J, Moita Luis F, Amigorena S, Savina A (2011) Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Cell 147(6):1355–1368

    Article  PubMed  CAS  Google Scholar 

  51. Savina A, Peres A, Cebrian I, Carmo N, Moita C, Hacohen N, Moita LF, Amigorena S (2009) The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8+ dendritic cells. Immunity 30(4):544–555

    Article  PubMed  CAS  Google Scholar 

  52. Belizaire R, Unanue ER (2009) Targeting proteins to distinct subcellular compartments reveals unique requirements for MHC class I and II presentation. Proc Natl Acad Sci USA 106(41):17463–17468

    Article  PubMed  CAS  Google Scholar 

  53. Shen L, Sigal LJ, Boes M, Rock KL (2004) Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity 21(2):155–165

    Article  PubMed  CAS  Google Scholar 

  54. Rock KL, Farfan-Arribas DJ, Shen L (2010) Proteases in MHC class I presentation and cross-presentation. J Immunol 184(1):9–15

    Article  PubMed  CAS  Google Scholar 

  55. Basha G, Lizee G, Reinicke AT, Seipp RP, Omilusik KD, Jefferies WA (2008) MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen loading in dendritic cells. PLoS One 3(9):e3247

    Article  PubMed  CAS  Google Scholar 

  56. Saveanu L, Carroll O, Weimershaus M, Guermonprez P, Firat E, Lindo V, Greer F, Davoust J, Kratzer R, Keller SR, Niedermann G, van Endert P (2009) IRAP identifies an endosomal compartment required for MHC class I cross-presentation. Science 325(5937):213–217

    Google Scholar 

  57. Houde M, Bertholet S, Gagnon E, Brunet S, Goyette G, Laplante A, Princiotta MF, Thibault P, Sacks D, Desjardins M (2003) Phagosomes are competent organelles for antigen cross-presentation. Nature 425:402

    Article  PubMed  CAS  Google Scholar 

  58. Guermonprez P, Saveanu L, Kleijmeer M, Davoust J, van Endert P, Amigorena S (2003) ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425(6956):397–402

    Article  PubMed  CAS  Google Scholar 

  59. Merzougui N, Kratzer R, Saveanu L, van Endert P (2011) A proteasome-dependent, TAP-independent pathway for cross-presentation of phagocytosed antigen. EMBO Rep 12(12):1257–1264

    Article  PubMed  CAS  Google Scholar 

  60. Ackerman AL, Giodini A, Cresswell P (2006) A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells. Immunity 25(4):607–617

    Article  PubMed  CAS  Google Scholar 

  61. Ackerman AL, Kyritsis C, Tampe R, Cresswell P (2003) Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens. Proc Natl Acad Sci USA 100(22):12889–12894

    Article  PubMed  CAS  Google Scholar 

  62. Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA (2005) Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 207(1):145–157

    Article  PubMed  CAS  Google Scholar 

  63. Ito T, Inaba M, Inaba K, Toki J, Sogo S, Iguchi T, Adachi Y, Yamaguchi K, Amakawa R, Valladeau J, Saeland S, Fukuhara S, Ikehara S (1999) A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. J Immunol 163(3):1409–1419

    PubMed  CAS  Google Scholar 

  64. Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V (2004) CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J Exp Med 199(4):567–579

    Article  PubMed  CAS  Google Scholar 

  65. Mouries J, Moron G, Schlecht G, Escriou N, Dadaglio G, Leclerc C (2008) Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation. Blood 112(9):3713–3722

    Article  PubMed  CAS  Google Scholar 

  66. Hoeffel G, Ripoche AC, Matheoud D, Nascimbeni M, Escriou N, Lebon P, Heshmati F, Guillet JG, Gannage M, Caillat-Zucman S, Casartelli N, Schwartz O, De la Salle H, Hanau D, Hosmalin A, Maranon C (2007) Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity 27(3):481–492

    Article  PubMed  CAS  Google Scholar 

  67. Nierkens S, den Brok MH, Garcia Z, Togher S, Wagenaars J, Wassink M, Boon L, Ruers TJ, Figdor CG, Schoenberger SP, Adema GJ, Janssen EM (2011) Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells. Cancer Res 71(20):6428–6437

    Article  PubMed  CAS  Google Scholar 

  68. Segura E, Albiston AL, Wicks IP, Chai SY, Villadangos JA (2009) Different cross-presentation pathways in steady-state and inflammatory dendritic cells. Proc Natl Acad Sci USA 106(48):20377–20381

    Article  PubMed  CAS  Google Scholar 

  69. Tobar JA, Gonzalez PA, Kalergis AM (2004) Salmonella escape from antigen presentation can be overcome by targeting bacteria to Fc{gamma} receptors on dendritic cells. J Immunol 173(6):4058–4065

    PubMed  CAS  Google Scholar 

  70. Pfeifer JD, Wick MJ, Roberts RL, Findlay K, Normark SJ, Harding CV (1993) Phagocytic processing of bacterial antigens for class I MHC presentation to T cells. Nature 361(6410):359–362

    Article  PubMed  CAS  Google Scholar 

  71. Svensson M, Wick MJ (1999) Classical MHC class I peptide presentation of a bacterial fusion protein by bone marrow-derived dendritic cells. Eur J Immunol 29(1):180–188

    Article  PubMed  CAS  Google Scholar 

  72. Palmowski MJ, Gileadi U, Salio M, Gallimore A, Millrain M, James E, Addey C, Scott D, Dyson J, Simpson E, Cerundolo V (2006) Role of immunoproteasomes in cross-presentation. J Immunol 177(2):983–990

    PubMed  CAS  Google Scholar 

  73. Lautscham G, Haigh T, Mayrhofer S, Taylor G, Croom-Carter D, Leese A, Gadola S, Cerundolo V, Rickinson A, Blake N (2003) Identification of a TAP-independent, immunoproteasome-dependent CD8+ T-cell epitope in Epstein-Barr virus latent membrane protein 2. J Virol 77(4):2757–2761

    Article  PubMed  CAS  Google Scholar 

  74. Hutchinson S, Sims S, O’Hara G, Silk J, Gileadi U, Cerundolo V, Klenerman P (2011) A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS One 6(2):e14646

    Article  PubMed  CAS  Google Scholar 

  75. Tu L, Moriya C, Imai T, Ishida H, Tetsutani K, Duan X, Murata S, Tanaka K, Shimokawa C, Hisaeda H, Himeno K (2009) Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection. Eur J Immunol 39(12):3385–3394

    Article  PubMed  CAS  Google Scholar 

  76. Burgdorf S, Lukacs-Kornek V, Kurts C (2006) The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation. J Immunol 176(11):6770–6776

    PubMed  CAS  Google Scholar 

  77. Burgdorf S, Kautz A, Bohnert V, Knolle PA, Kurts C (2007) Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 316(5824):612–616

    Article  PubMed  CAS  Google Scholar 

  78. Burgdorf S, Schuette V, Semmling V, Hochheiser K, Lukacs-Kornek V, Knolle PA, Kurts C (2010) Steady-state cross-presentation of OVA is mannose receptor-dependent but inhibitable by collagen fragments. Proc Natl Acad Sci USA 107(13):E48–E49

    Article  PubMed  CAS  Google Scholar 

  79. Zehner M, Chasan AI, Schuette V, Embgenbroich M, Quast T, Kolanus W, Burgdorf S (2011) Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation. Proc Natl Acad Sci USA 108(24):9933–9938

    Article  PubMed  CAS  Google Scholar 

  80. Kratzer R, Mauvais F-X, Burgevin A, Barilleau E, van Endert P (2010) Fusion proteins for versatile antigen targeting to cell-surface receptors reveal differential capacity to prime immune responses. J Immunol 184(12):6855–6864

    Article  PubMed  CAS  Google Scholar 

  81. Tsuji T, Matsuzaki J, Kelly MP, Ramakrishna V, Vitale L, He L-Z, Keler T, Odunsi K, Old LJ, Ritter G, Gnjatic S (2010) Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity. J Immunol 186(2):1218–1227

    Article  PubMed  CAS  Google Scholar 

  82. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM (2004) In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 199(6):815–824

    Article  PubMed  CAS  Google Scholar 

  83. Vremec D, Shortman K (1997) Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol 159(2):565–573

    PubMed  CAS  Google Scholar 

  84. del Hoyo GM, Martin P, Arias CF, Martin AR, Ardavin C (2002) CD8alpha+ dendritic cells originate from the CD8alpha- dendritic cell subset by a maturation process involving CD8alpha, DEC-205, and CD24 up-regulation. Blood 99(3):999–1004

    Article  Google Scholar 

  85. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8 + T cell tolerance. J Exp Med 196(12):1627–1638

    Article  PubMed  CAS  Google Scholar 

  86. Amigorena S, Bonnerot C (1999) Fc receptor signaling and trafficking: a connection for antigen processing. Immunol Rev 172:279–284

    Article  PubMed  CAS  Google Scholar 

  87. Regnault A, Lankar D, Lacabanne V, Rodriguez A, Thery C, Rescigno M, Saito T, Verbeek S, Bonnerot C, Ricciardi-Castagnoli P, Amigorena S (1999) Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189(2):371–380

    Article  PubMed  CAS  Google Scholar 

  88. Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S (1999) Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol 1(6):362–368

    Article  PubMed  CAS  Google Scholar 

  89. Nimmerjahn F, Ravetch JV (2010) Antibody-mediated modulation of immune responses. Immunol Rev 236(1):265–275

    Article  PubMed  CAS  Google Scholar 

  90. Nimmerjahn F, Ravetch JV (2008) Fc-gamma receptors as regulators of immune responses. Nat Rev Immunol 8(1):34–47

    Article  PubMed  CAS  Google Scholar 

  91. Kiener PA, Rankin BM, Burkhardt AL, Schieven GL, Gilliland LK, Rowley RB, Bolen JB, Ledbetter JA (1993) Cross-linking of Fc gamma receptor I (Fc gamma RI) and receptor II (Fc gamma RII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase. J Biol Chem 268(32):24442–24448

    PubMed  CAS  Google Scholar 

  92. Kurosaki T, Johnson SA, Pao L, Sada K, Yamamura H, Cambier JC (1995) Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling. J Exp Med 182(6):1815–1823

    Article  PubMed  CAS  Google Scholar 

  93. Ghazizadeh S, Bolen JB, Fleit HB (1994) Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells. J Biol Chem 269(12):8878–8884

    PubMed  CAS  Google Scholar 

  94. Wang AV, Scholl PR, Geha RS (1994) Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn. J Exp Med 180(3):1165–1170

    Article  PubMed  CAS  Google Scholar 

  95. Huang MM, Indik Z, Brass LF, Hoxie JA, Schreiber AD, Brugge JS (1992) Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII. J Biol Chem 267(8):5467–5473

    PubMed  CAS  Google Scholar 

  96. Indik ZK, Park JG, Hunter S, Schreiber AD (1995) The molecular dissection of Fc gamma receptor-mediated phagocytosis. Blood 86(12):4389–4399

    PubMed  CAS  Google Scholar 

  97. Indik ZK, Park J-G, Hunter S, Mantaring M, Schreiber AD (1995) Molecular dissection of Fc-gamma receptor-mediated phagocytosis. Immunol Lett 44(2–3):133–138

    Article  PubMed  CAS  Google Scholar 

  98. Mitchell MA, Huang MM, Chien P, Indik ZK, Pan XQ, Schreiber AD (1994) Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis. Blood 84(6):1753–1759 (Published erratum appears in Blood 1994 Nov 1;84(9):3252)

    PubMed  CAS  Google Scholar 

  99. Breunis WB, van Mirre E, Bruin M, Geissler J, de Boer M, Peters M, Roos D, de Haas M, Koene HR, Kuijpers TW (2008) Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood 111(3):1029–1038

    Article  PubMed  CAS  Google Scholar 

  100. Ono M, Bolland S, Tempst P, Ravetch JV (1996) Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fe[gamma]RIIB. Nature 383(6597):263–266

    Article  PubMed  CAS  Google Scholar 

  101. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang H-M, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz H-J (2007) FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor-expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 25(24):3712–3718

    Article  PubMed  CAS  Google Scholar 

  102. Binstadt BA, Geha RS, Bonilla FA (2003) IgG Fc receptor polymorphisms in human disease: implications for intravenous immunoglobulin therapy. J Allergy Clin Immunol 111(4):697–703

    Article  PubMed  CAS  Google Scholar 

  103. Bournazos S, Woof JM, Hart SP, Dransfield I (2009) Functional and clinical consequences of Fc receptor polymorphic and copy number variants. Clin Exp Immunol 157(2):244–254

    Article  PubMed  CAS  Google Scholar 

  104. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daeron M (2009) Specificity and affinity of human Fc-gamma receptors and their polymorphic variants for human IgG subclasses. Blood 113(16):3716–3725

    Article  PubMed  CAS  Google Scholar 

  105. Simister NE, Mostov KE (1989) An Fc receptor structurally related to MHC class I antigens. Nature 337(6203):184–187

    Article  PubMed  CAS  Google Scholar 

  106. Simister NE, Rees AR (1985) Isolation and characterization of an Fc receptor from neonatal rat small intestine. Eur J Immunol 15(7):733–738

    Article  PubMed  CAS  Google Scholar 

  107. Claypool SM, Dickinson BL, Yoshida M, Lencer WI, Blumberg RS (2002) Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin. J Biol Chem 277(31):28038–28050

    Article  PubMed  CAS  Google Scholar 

  108. Baker K, Qiao SW, Kuo T, Kobayashi K, Yoshida M, Lencer WI, Blumberg RS (2009) Immune and non-immune functions of the (not so) neonatal Fc receptor FcRn. Semin Immunopathol 31(2):223–236

    Article  PubMed  CAS  Google Scholar 

  109. Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer WI, Blumberg RS (2010) Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 30(6):777–789

    Google Scholar 

  110. Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (2003) The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197(3):315–322

    Article  PubMed  CAS  Google Scholar 

  111. Leach JL, Sedmak DD, Osborne JM, Rahill B, Lairmore MD, Anderson CL (1996) Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport. J Immunol 157(8):3317–3322

    PubMed  CAS  Google Scholar 

  112. Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, Petkova S, Avanessian L, Choi EY, Shaffer DJ, Eden PA, Anderson CL (2003) The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 170(7):3528–3533

    PubMed  CAS  Google Scholar 

  113. Blumberg RS, Koss T, Story CM, Barisani D, Polischuk J, Lipin A, Pablo L, Green R, Simister NE (1995) A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. J Clin Invest 95(5):2397–2402

    Article  PubMed  CAS  Google Scholar 

  114. Dickinson BL, Badizadegan K, Wu Z, Ahouse JC, Zhu X, Simister NE, Blumberg RS, Lencer WI (1999) Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 104(7):903–911

    Article  PubMed  CAS  Google Scholar 

  115. Kobayashi K, Qiao SW, Yoshida M, Baker K, Lencer WI, Blumberg RS (2009) An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice. Gastroenterology 137(5): 1746–1756 (e1741)

    Google Scholar 

  116. Raghavan M, Bjorkman PJ (1996) Fc receptors and their interactions with immunoglobulins. Annu Rev Cell Dev Biol 12(1):181–220

    Article  PubMed  CAS  Google Scholar 

  117. Martin WL, West AP, Jr., Gan L, Bjorkman PJ (2001) Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 7(4): 867–877

    Google Scholar 

  118. Newton EE, Wu Z, Simister NE (2005) Characterization of basolateral-targeting signals in the neonatal Fc receptor. J Cell Sci 118(Pt 11):2461–2469

    Article  PubMed  CAS  Google Scholar 

  119. Stefaner I, Praetor A, Hunziker W (1999) Nonvectorial surface transport, endocytosis via a Di-leucine-based motif, and bidirectional transcytosis of chimera encoding the cytosolic tail of rat FcRn expressed in Madin-Darby canine kidney cells. J Biol Chem 274(13):8998–9005

    Article  PubMed  CAS  Google Scholar 

  120. McCarthy KM, Lam M, Subramanian L, Shakya R, Wu Z, Newton EE, Simister NE (2001) Effects of mutations in potential phosphorylation sites on transcytosis of FcRn. J Cell Sci 114(Pt 8):1591–1598

    PubMed  CAS  Google Scholar 

  121. de Jong JM, Schuurhuis DH, Ioan-Facsinay A, van der Voort EI, Huizinga TW, Ossendorp F, Toes RE, Verbeek JS (2006) Murine Fc receptors for IgG are redundant in facilitating presentation of immune complex derived antigen to CD8+ T cells in vivo. Mol Immunol 43(13):2045–2050

    Article  PubMed  CAS  Google Scholar 

  122. Canetti C, Aronoff DM, Choe M, Flamand N, Wettlaufer S, Toews GB, Chen G-H, Peters-Golden M (2006) Differential regulation by leukotrienes and calcium of Fc-gamma receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages. J Leukoc Biol 79(6):1234–1241

    Article  PubMed  CAS  Google Scholar 

  123. Fanger NA, Voigtlaender D, Liu C, Swink S, Wardwell K, Fisher J, Graziano RF, Pfefferkorn LC, Guyre PM (1997) Characterization of expression, cytokine regulation, and effector function of the high affinity IgG receptor Fc gamma RI (CD64) expressed on human blood dendritic cells. J Immunol 158(7):3090–3098

    PubMed  CAS  Google Scholar 

  124. den Haan JMM, Bevan MJ (2002) Constitutive versus activation-dependent cross-presentation of immune complexes by CD8+ and CD8− dendritic cells in vivo. J Exp Med 196(6):817–827

    Article  CAS  Google Scholar 

  125. Giodini A, Rahner C, Cresswell P (2009) Receptor-mediated phagocytosis elicits cross-presentation in nonprofessional antigen-presenting cells. Proc Natl Acad Sci USA 106(9):3324–3329

    Article  PubMed  CAS  Google Scholar 

  126. Flores M, Desai DD, Downie M, Liang B, Reilly MP, McKenzie SE, Clynes R (2009) Dominant expression of the inhibitory Fc{gamma}RIIB Prevents antigen presentation by murine plasmacytoid dendritic cells. J Immunol 183(11):7129–7139

    Article  PubMed  CAS  Google Scholar 

  127. Boruchov AM, Heller G, Veri M-C, Bonvini E, Ravetch JV, Young JW (2005) Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J Clin Invest 115(10):2914

    Article  PubMed  CAS  Google Scholar 

  128. Desai DD, Harbers SO, Flores M, Colonna L, Downie MP, Bergtold A, Jung S, Clynes R (2007) Fc-gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. J Immunol 178(10):6217–6226

    PubMed  CAS  Google Scholar 

  129. Signorino E, Brusa D, Granata R, Malavasi F, Ferrone S, Matera L (2007) Contribution of dendritic cells’ FcgammaRI and FcgammaRIII to cross-presentation of tumor cells opsonized with the anti-MHC class I monoclonal antibodies. Cancer Biol Ther 6(12):1932–1937

    Article  PubMed  CAS  Google Scholar 

  130. Dai X, Jayapal M, Tay HK, Reghunathan R, Lin G, Too CT, Lim YT, Chan SH, Kemeny DM, Floto RA, Smith KGC, Melendez AJ, MacAry PA (2009) Differential signal transduction, membrane trafficking, and immune effector functions mediated by Fc{gamma}RI versus Fc{gamma}RIIa. Blood 114(2):318–327

    Article  PubMed  CAS  Google Scholar 

  131. Sedlik C, Orbach D, Veron P, Schweighoffer E, Colucci F, Gamberale R, Ioan-Facsinay A, Verbeek S, Ricciardi-Castagnoli P, Bonnerot C, Tybulewicz VLJ, Di Santo J, Amigorena S (2003) A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation. J Immunol 170(2):846–852

    PubMed  CAS  Google Scholar 

  132. Pricop L, Redecha P, Teillaud J-L, Frey J, Fridman WH, Sautes-Fridman C, Salmon JE (2001) Differential modulation of stimulatory and inhibitory Fc-gamma receptors on human monocytes by Th1 and Th2 cytokines. J Immunol 166(1):531–537

    PubMed  CAS  Google Scholar 

  133. Barrionuevo P, Beigier-Bompadre M, Ilarregui JM, Toscano MA, Bianco GA, Isturiz MA, Rabinovich GA (2007) A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol 178(1):436–445

    PubMed  CAS  Google Scholar 

  134. Beekman JM, Bakema JE, van de Winkel JGJ, Leusen JHW (2004) Direct interaction between Fc-gamma RI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity. Proc Natl Acad Sci USA 101(28):10392–10397

    Article  PubMed  CAS  Google Scholar 

  135. Kim SH, Visser A, Cruijsen C, van der Velden AW, Boes M (2008) Recruitment of Rab27a to phagosomes controls microbial antigen cross-presentation by dendritic cells. Infect Immun 76(11):5373–5380

    Article  PubMed  CAS  Google Scholar 

  136. van Montfoort N, de Jong JMH, Schuurhuis DH, van der Voort EIH, Camps MGM, Huizinga TWJ, van Kooten C, Daha MR, Verbeek JS, Ossendorp F, Toes REM (2007) A novel role of complement factor C1q in augmenting the presentation of antigen captured in immune complexes to CD8+ T lymphocytes. J Immunol 178(12):7581–7586

    PubMed  Google Scholar 

  137. Benitez-Ribas D, Tacken P, Punt CJA, de Vries IJM, Figdor CG (2008) Activation of human plasmacytoid dendritic cells by TLR9 impairs Fc-gamma RII-mediated uptake of immune complexes and presentation by MHC class II. J Immunol 181(8):5219–5224

    PubMed  CAS  Google Scholar 

  138. Bevaart L, Van Ojik HH, Sun AW, Sulahian TH, Leusen JH, Weiner GJ, Van De Winkel JG, Van Vugt MJ (2004) CpG oligodeoxynucleotides enhance FcgammaRI-mediated cross presentation by dendritic cells. Int Immunol 16(8):1091–1098

    Article  PubMed  CAS  Google Scholar 

  139. Boule MW, Broughton C, Mackay F, Akira S, Marshak-Rothstein A, Rifkin IR (2004) Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J Exp Med 199(12):1631–1640

    Article  PubMed  CAS  Google Scholar 

  140. Oh JZ, Kurche JS, Burchill MA, Kedl RM (2010) TLR7 enables cross-presentation by multiple dendritic cell subsets through a type I IFN-dependent pathway. Blood 118(11):3028–3038

    Article  CAS  Google Scholar 

  141. de Brito C, Tomkowiak M, Ghittoni R, Caux C, Leverrier Y, Marvel J (2011) CpG promotes cross-presentation of dead cell-associated antigens by pre-CD8alpha +dendritic cells. J Immunol 186(3):1503–1511

    Article  PubMed  CAS  Google Scholar 

  142. Yan M, Peng J, Jabbar IA, Liu X, Filgueira L, Frazer IH, Thomas R (2004) Despite differences between dendritic cells and Langerhans cells in the mechanism of papillomavirus-like particle antigen uptake, both cells cross-prime T cells. Virology 324(2):297–310

    Article  PubMed  CAS  Google Scholar 

  143. Vyas JM, Van der Veen AG, Ploegh HL (2008) The known unknowns of antigen processing and presentation. Nat Rev Immunol 8(8):607–618

    Article  PubMed  CAS  Google Scholar 

  144. Segura E, Villadangos JA (2011) A modular and combinatorial view of the antigen cross-presentation pathway in dendritic cells. Traffic 12(12):1677–1685

    Article  PubMed  CAS  Google Scholar 

  145. Claypool SM, Dickinson BL, Wagner JS, Johansen FE, Venu N, Borawski JA, Lencer WI, Blumberg RS (2004) Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor. Mol Biol Cell 15(4):1746–1759

    Article  PubMed  CAS  Google Scholar 

  146. Yoshida M, Claypool SM, Wagner JS, Mizoguchi E, Mizoguchi A, Roopenian DC, Lencer WI, Blumberg RS (2004) Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity 20(6):769–783

    Article  PubMed  CAS  Google Scholar 

  147. Spiekermann GM, Finn PW, Ward ES, Dumont J, Dickinson BL, Blumberg RS, Lencer WI (2002) Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med 196(3):303–310

    Article  PubMed  CAS  Google Scholar 

  148. Bitonti AJ, Dumont JA (2006) Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv Drug Deliv Rev 58(9–10):1106–1118

    Article  PubMed  CAS  Google Scholar 

  149. Bitonti AJ, Dumont JA, Low SC, Peters RT, Kropp KE, Palombella VJ, Stattel JM, Lu Y, Tan CA, Song JJ, Garcia AM, Simister NE, Spiekermann GM, Lencer WI, Blumberg RS (2004) Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci USA 101(26):9763–9768

    Article  PubMed  CAS  Google Scholar 

  150. Kim KJ, Fandy TE, Lee VH, Ann DK, Borok Z, Crandall ED (2004) Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 287(3):L616–L622

    Article  PubMed  CAS  Google Scholar 

  151. Schlachetzki F, Zhu C, Pardridge WM (2002) Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem 81(1):203–206

    Article  PubMed  CAS  Google Scholar 

  152. Story CM, Mikulska JE, Simister NE (1994) A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus. J Exp Med 180(6):2377–2381

    Article  PubMed  CAS  Google Scholar 

  153. Firan M, Bawdon R, Radu C, Ober RJ, Eaken D, Antohe F, Ghetie V, Ward ES (2001) The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans. Int Immunol 13(8):993–1002

    Article  PubMed  CAS  Google Scholar 

  154. Telleman P, Junghans RP (2000) The role of the Brambell receptor (FcRB) in liver: protection of endocytosed immunoglobulin G (IgG) from catabolism in hepatocytes rather than transport of IgG to bile. Immunology 100(2):245–251

    Article  PubMed  CAS  Google Scholar 

  155. Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, Wang Y, Robert C, Wu B, Smith PD, Lencer WI, Blumberg RS (2001) MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol 166(5):3266–3276

    PubMed  CAS  Google Scholar 

  156. Yates RM, Hermetter A, Russell DG (2005) The kinetics of phagosome maturation as a function of phagosome/lysosome fusion and acquisition of hydrolytic activity. Traffic 6(5):413–420

    Article  PubMed  CAS  Google Scholar 

  157. Liu X, Lu L, Yang Z, Palaniyandi S, Zeng R, Gao L-Y, Mosser DM, Roopenian DC, Zhu X (2011) The neonatal FcR-mediated presentation of immune-complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells. J Immunol 186(8):4674–4686

    Article  PubMed  CAS  Google Scholar 

  158. den Haan JMM, Lehar SM, Bevan MJ (2000) CD8+ but not CD8− dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192(12):1685–1696

    Article  Google Scholar 

  159. Kita H, Ansari AA, He X-S, Lian Z-X, Van de Water J, Coppel RL, Luketic V, Kaplan M, Inamori H, Isoda N, Sugano K, Imawari M, Gershwin ME (2003) Proteasome is required for class I-restricted presentation by Fc-gamma receptor-mediated endocytosis in primary biliary cirrhosis. J Autoimmun 21(2):175–182

    Article  CAS  Google Scholar 

  160. van Montfoort N, Camps MG, Khan S, Filippov DV, Weterings JJ, Griffith JM, Geuze HJ, van Hall T, Verbeek JS, Melief CJ, Ossendorp F (2009) Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity. Proc Natl Acad Sci USA 106(16):6730–6735

    Article  PubMed  Google Scholar 

  161. Harbers SO, Crocker A, Catalano G, D’Agati V, Jung S, Desai DD, Clynes R (2007) Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J Clin Invest 117(5):1361–1369

    Article  PubMed  CAS  Google Scholar 

  162. Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, Bredin F, Rickman HM, Ratlamwala H, Hatton A, Rayner TF, Parkes M, Smith KGC (2011) Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest 121(10):4170–4179

    Article  PubMed  CAS  Google Scholar 

  163. Clynes R (2007) Protective mechanisms of IVIG. Curr Opin Immunol 19(6):646–651

    Article  PubMed  CAS  Google Scholar 

  164. Hansen RJ, Balthasar JP (2002) Intravenous immunoglobulin mediates an increase in anti-platelet antibody clearance via the FcRn receptor. Thromb Haemost 88(6):898–899

    PubMed  CAS  Google Scholar 

  165. Li N, Zhao M, Hilario-Vargas J, Prisayanh P, Warren S, Diaz LA, Roopenian DC, Liu Z (2005) Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases. J Clin Invest 115(12):3440–3450

    Article  PubMed  CAS  Google Scholar 

  166. Nimmerjahn F, Ravetch JV (2007) The antiinflammatory activity of IgG: the intravenous IgG paradox. J Exp Med 204(1):11–15

    Article  PubMed  CAS  Google Scholar 

  167. Nimmerjahn F, Ravetch JV (2008) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26(1):513–533

    Article  PubMed  CAS  Google Scholar 

  168. Colonna L, Catalano G, Chew C, D’Agati V, Thomas JW, Wong FS, Schmitz J, Masuda ES, Reizis B, Tarakhovsky A, Clynes R (2010) Therapeutic targeting of Syk in autoimmune diabetes. J Immunol 185(3):1532–1543

    Article  PubMed  CAS  Google Scholar 

  169. Herrada AA, Contreras FJ, Tobar JA, Pacheco R, Kalergis AM (2007) Immune complex-induced enhancement of bacterial antigen presentation requires Fc-gamma Receptor III expression on dendritic cells. Proc Natl Acad Sci USA 104(33):13402–13407

    Article  PubMed  CAS  Google Scholar 

  170. Villinger F, Mayne AE, Bostik P, Mori K, Jensen PE, Ahmed R, Ansari AA (2003) Evidence for antibody-mediated enhancement of simian immunodeficiency virus (SIV) Gag antigen processing and cross presentation in SIV-infected rhesus macaques. J Virol 77(1):10–24

    Article  PubMed  CAS  Google Scholar 

  171. Hervouet C, Luci C, Cuburu N, Cremel M, Bekri S, Vimeux L, Maranon C, Czerkinsky C, Hosmalin A, Anjuere F (2010) Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract. Vaccine 28(34):5582–5590

    Article  PubMed  CAS  Google Scholar 

  172. Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV (2002) Antitumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. J Exp Med 195(1):125–133

    Article  PubMed  CAS  Google Scholar 

  173. Wallace PK, Tsang KY, Goldstein J, Correale P, Jarry TM, Schlom J, Guyre PM, Ernstoff MS, Fanger MW (2001) Exogenous antigen targeted to FcgammaRI on myeloid cells is presented in association with MHC class I. J Immunol Methods 248(1–2):183–194

    Article  PubMed  CAS  Google Scholar 

  174. Rafiq K, Bergtold A, Clynes R (2002) Immune complex-mediated antigen presentation induces tumor immunity. J Clin Invest 110(1):71

    PubMed  CAS  Google Scholar 

  175. Akiyama K, Ebihara S, Yada A, Matsumura K, Aiba S, Nukiwa T, Takai T (2003) Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells. J Immunol 170(4):1641–1648

    PubMed  CAS  Google Scholar 

  176. Shen L, van Egmond M, Siemasko K, Gao H, Wade T, Lang ML, Clark M, van de Winkel JGJ, Wade WF (2001) Presentation of ovalbumin internalized via the immunoglobulin-A Fc receptor is enhanced through Fc receptor gamma-chain signaling. Blood 97(1):205–213

    Article  PubMed  CAS  Google Scholar 

  177. Chen Y-W, Lang ML, Wade WF (2004) Protein kinase C-alpha and -delta are required for Fc-alphaR (CD89) trafficking to MHC class II compartments and Fc-alphaR-mediated antigen presentation. Traffic 5(8):577–594

    Article  PubMed  CAS  Google Scholar 

  178. Sallmann E, Reininger B, Brandt S, Duschek N, Hoflehner E, Garner-Spitzer E, Platzer B, Dehlink E, Hammer M, Holcmann M, Oettgen HC, Wiedermann U, Sibilia M, Fiebiger E, Rot A, Maurer D (2011) High-affinity IgE receptors on dendritic cells exacerbate Th2-dependent inflammation. J Immunol 187(1):164–171

    Article  PubMed  CAS  Google Scholar 

  179. Getahun A, Hjelm F, Heyman B (2005) IgE enhances antibody and T cell responses in vivo via CD23+ B cells. J Immunol 175(3):1473–1482

    PubMed  CAS  Google Scholar 

  180. Henningsson F, Ding Z, Dahlin JS, Linkevicius M, Carlsson F, Gronvik K-O, Hallgren J, Heyman B (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(7):e21760

    Article  PubMed  CAS  Google Scholar 

  181. Platzer B, Dehlink E, Turley SJ, Fiebiger E (2012) How to connect an IgE-driven response with CTL activity? Cancer Immunol Immunother (in press)

  182. Ke Y, Kapp JA (1996) Exogenous antigens gain access to the major histocompatibility complex class I processing pathway in B cells by receptor-mediated uptake. J Exp Med 184(3):1179–1184

    Article  PubMed  CAS  Google Scholar 

  183. Abboud G, Staumont-Salle D, Kanda A, Roumier T, Deruytter N, Lavogiez C, Fleury S, Remy P, Papin J-P, Capron M, Dombrowicz D (2009) FceRI and FcgRIII/CD16 differentially regulate atopic dermatitis in mice. J Immunol 182(10):6517–6526

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

K.B. was supported by the Canadian Institutes of Health Research. T.R. is supported by the Deutsche Forschungsgemeinschaft (RA 2040/1-1). E.F is supported by NIH AI075037. W.I.L. is supported by NIH DK084424. R.S.B is supported by NIH DK053056, DK053162, DK088199 and DK044319. W.I.L. and R.S.B. are also supported by the Harvard Digestive Diseases Center (NIH P30DK034854). The authors have no conflicting financial interests.

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  1. Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Kristi Baker, Timo Rath & Richard S. Blumberg

  2. Division of Gastroenterology and Nutrition, Children’s Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA

    Wayne I. Lencer & Edda Fiebiger

  3. Harvard Digestive Diseases Center, Boston, MA, 02115, USA

    Wayne I. Lencer, Edda Fiebiger & Richard S. Blumberg

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  1. Kristi Baker
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Correspondence to Richard S. Blumberg.

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Baker, K., Rath, T., Lencer, W.I. et al. Cross-presentation of IgG-containing immune complexes. Cell. Mol. Life Sci. 70, 1319–1334 (2013). https://doi.org/10.1007/s00018-012-1100-8

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