Immunologic Research

, Volume 53, Issue 1–3, pp 91–107 | Cite as

The specialized roles of immature and mature dendritic cells in antigen cross-presentation

  • Richard A. Hopkins
  • John E. ConnollyEmail author
Singapore Immunology Network


Exogenous antigen cross-presentation is integral to the stimulation of cytotoxic T-lymphocytes against viruses and tumors. Central to this process are dendritic cells (DCs), which specialize in cross-presentation. DCs may be considered to exist in two radically different states of activation, generally referred to as immature and mature. In each of these states, the cell has a series of separate and specialized abilities for the induction of T-cell immunity. In the immature state, the DC is adept in surveying the periphery, acquiring and storing antigen, but has a limited capacity for direct T-cell activation. During a brief and defined window of time following DC stimulation, nearly every aspect of antigen handling changes, as it transitions from an entity focused on protein preservation to one capable of efficient cross-presentation. It is this time period and the underlying molecular mechanisms active here, which form the core of our studies on cross-presentation.


Antigen preservation C-type lectins Dendritic cell targeting Endocytic trafficking Receptor trafficking 



RH and JC are supported by SIgN core funds. JC is supported by BMRC and Horizontal Program in Infectious Disease. The authors wish to thank Jessica Chen and David Skibinski for editorial review. We would also like to thank Ralph Steinman for his support and guidance.


  1. 1.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–252.PubMedCrossRefGoogle Scholar
  2. 2.
    Shortman K, Liu YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002;2(3):151–161.PubMedCrossRefGoogle Scholar
  3. 3.
    Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9(1):271–296.PubMedCrossRefGoogle Scholar
  4. 4.
    Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449(7161):419–426.PubMedCrossRefGoogle Scholar
  5. 5.
    Bevan MJ. 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. 1976;143(5):1283–1288.PubMedCrossRefGoogle Scholar
  6. 6.
    Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell. 2001;106(3):255–258.PubMedCrossRefGoogle Scholar
  7. 7.
    Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, Galán JE, Mellman I. Developmental control of endocytosis in dendritic cells by Cdc42. Cell. 2000;102(3):325–334.PubMedCrossRefGoogle Scholar
  8. 8.
    Trombetta ES. Activation of lysosomal function during dendritic cell maturation. Science (New York, NY). 2003;299(5611):1400–1403.CrossRefGoogle Scholar
  9. 9.
    West MA, Prescott AR, Chan KM, Zhou Z, Rose-John S, Scheller J, Watts C. TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent. J Cell Biol. 2008;182(5):993–1005.PubMedCrossRefGoogle Scholar
  10. 10.
    Weck MM, Grünebach F, Werth D, Sinzger C, Bringmann A, Brossart P. TLR ligands differentially affect uptake and presentation of cellular antigens. Blood. 2007;109(9):3890–3894.PubMedCrossRefGoogle Scholar
  11. 11.
    Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR, Qin S, Lanzavecchia A. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Euro J Immunol. 1998;28(9):2760–2769.CrossRefGoogle Scholar
  12. 12.
    Sozzani S, Luini W, Borsatti A, Polentarutti N, Zhou D, Piemonti L, D’Amico G, Power CA, Wells TN, Gobbi M, Allavena P, Mantovani A. Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. J Immunol (Baltimore, Md : 1950). 1997;159(4):1993–2000.Google Scholar
  13. 13.
    Watarai H, Hinohara A, Nagafune J, Nakayama T, Taniguchi M, Yamaguchi Y. Plasma membrane-focused proteomics: dramatic changes in surface expression during the maturation of human dendritic cells. Proteomics. 2005;5(15):4001–4011.PubMedCrossRefGoogle Scholar
  14. 14.
    van Helden SFG, Krooshoop DJEB, Broers KCM, Raymakers RAP, Figdor CG, van Leeuwen FN. A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation. J Immunol (Baltimore, Md : 1950). 2006;177(3):1567–1574.Google Scholar
  15. 15.
    Buccione R, Orth JD, McNiven MA. Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol. 2004;5(8):647–657.PubMedCrossRefGoogle Scholar
  16. 16.
    Zamir E, Katz M, Posen Y, Erez N, Yamada KM, Katz BZ, Lin S, Lin DC, Bershadsky A, Kam Z, Geiger B. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat Cell Biol. 2000;2(4):191–196.PubMedCrossRefGoogle Scholar
  17. 17.
    Linder S, Aepfelbacher M. Podosomes: adhesion hot-spots of invasive cells. Trend Cell Biol. 2003;13(7):376–385.CrossRefGoogle Scholar
  18. 18.
    Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, Whitney JA, Connolly J, Banchereau J, Mellman I. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity. 2007;27(4):610–624.PubMedCrossRefGoogle Scholar
  19. 19.
    Kohrgruber N, Gröger M, Meraner P, Kriehuber E, Petzelbauer P, Brandt S, Stingl G, Rot A, Maurer D. Plasmacytoid dendritic cell recruitment by immobilized CXCR3 ligands. J Immunol (Baltimore, Md : 1950). 2004;173(11):6592–6602.Google Scholar
  20. 20.
    Schuster P, Donhauser N, Pritschet K, Ries M, Haupt S, Kittan NA, Korn K, Schmidt B. Co-ordinated regulation of plasmacytoid dendritic cell surface receptors upon stimulation with herpes simplex virus type 1. Immunology. 2010;129(2):234–247.PubMedCrossRefGoogle Scholar
  21. 21.
    Janeway CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symp Quant Biol. 1989;54(Pt 1):1–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in drosophila adults. Cell. 1996;86(6):973–983.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee MS, Kim YJ. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem. 2007;76:447–480.PubMedCrossRefGoogle Scholar
  24. 24.
    Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194(6):863–869.PubMedCrossRefGoogle Scholar
  25. 25.
    Visintin A, Mazzoni A, Spitzer JH, Wyllie DH, Dower SK, Segal DM. Regulation of toll-like receptors in human monocytes and dendritic cells. J Immunol (Baltimore, Md : 1950). 2001;166(1):249–255.Google Scholar
  26. 26.
    Nilsen NJ, Deininger S, Nonstad U, Skjeldal F, Husebye H, Rodionov D, von Aulock S, Hartung T, Lien E, Bakke O, Espevik T. Cellular trafficking of lipoteichoic acid and Toll-like receptor 2 in relation to signaling: role of CD14 and CD36. J Leukoc Biol. 2008;84(1):280–291.PubMedCrossRefGoogle Scholar
  27. 27.
    Latz E, Visintin A, Lien E, Fitzgerald KA, Monks BG, Kurt-Jones EA, Golenbock DT, Espevik T. Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction. J Biol Chem. 2002;277(49):47,834–47,843.CrossRefGoogle Scholar
  28. 28.
    Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2010;32(3):305–315.PubMedCrossRefGoogle Scholar
  29. 29.
    Yoneyama M, Fujita T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev. 2009;227(1):54–65.PubMedCrossRefGoogle Scholar
  30. 30.
    Torii I, Morikawa S, Nagasaki M, Nokano A, Morikawa K. Differential endocytotic characteristics of a novel human B/DC cell line HBM-Noda: effective macropinocytic and phagocytic function rather than scavenging function. Immunology. 2001;103(1):70–80.PubMedCrossRefGoogle Scholar
  31. 31.
    West MA, Antoniou AN, Prescott AR, Azuma T, Kwiatkowski DJ, Watts C. Membrane ruffling, macropinocytosis and antigen presentation in the absence of gelsolin in murine dendritic cells. Euro J Immunol. 1999;29(11):3450–3455.CrossRefGoogle Scholar
  32. 32.
    Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature. 2003;422(6927):37–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Norbury CC. Drinking a lot is good for dendritic cells. Immunology. 2006;117(4):443–451.PubMedCrossRefGoogle Scholar
  34. 34.
    Burgdorf S, Kautz A, Böhnert V, Knolle PA, Kurts C. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science (New York, NY). 2007;316(5824):612–616.CrossRefGoogle Scholar
  35. 35.
    Le Roux D, Le Bon A, Dumas A, Taleb K, Sachse M, Sikora R, Julithe M, Benmerah A, Bismuth G, Niedergang F. Antigen stored in dendritic cells after macropinocytosis is released unprocessed from late endosomes to target B cells. Blood 2011;119(1):95–105.Google Scholar
  36. 36.
    de Baey A, Lanzavecchia A. The role of aquaporins in dendritic cell macropinocytosis. J Exp Med. 2000;191(4):743–748.PubMedCrossRefGoogle Scholar
  37. 37.
    King LS, Agre P. Pathophysiology of the aquaporin water channels. Annu Rev Physiol. 1996;58:619–648.PubMedCrossRefGoogle Scholar
  38. 38.
    Anderson RG. The caveolae membrane system. Annu Rev Biochem. 1998;67:199–225.PubMedCrossRefGoogle Scholar
  39. 39.
    Khan S, Bijker MS, Weterings JJ, Tanke HJ, Adema GJ, van Hall T, Drijfhout JW, Melief CJM, Overkleeft HS, van der Marel GA, Filippov DV, van der Burg SH, Ossendorp F. Distinct uptake mechanisms but similar intracellular processing of two different toll-like receptor ligand-peptide conjugates in dendritic cells. J Biol Chem. 2007;282(29):21,145–21,159.CrossRefGoogle Scholar
  40. 40.
    Maxfield FR, McGraw TE. Endocytic recycling. Nat Rev Mol Cell Biol. 2004;5(2):121–132.PubMedCrossRefGoogle Scholar
  41. 41.
    Huotari J, Helenius A. Endosome maturation. EMBO J. 2011;30(17):3481–3500.PubMedCrossRefGoogle Scholar
  42. 42.
    Agola J, Jim P, Ward H, Basuray S, Wandinger-Ness A. Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities. Clin Genetics 2011;80(4):305–318.Google Scholar
  43. 43.
    Ferret-Bernard S, Castro-Borges W, Dowle AA, Sanin DE, Cook PC, Turner JD, Macdonald AS, Thomas JR, Mountford AP. Plasma membrane proteomes of differentially matured dendritic cells identified by LC-MS/MS combined with iTRAQ labelling. J Proteomics 2011;75(3):938–948.Google Scholar
  44. 44.
    Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111(7):927–930.PubMedCrossRefGoogle Scholar
  45. 45.
    Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL, Nussenzweig M, Steinman RM. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J Cell Biol. 2000;151(3):673–684.PubMedCrossRefGoogle Scholar
  46. 46.
    Jiang W, Swiggard WJ, Heufler C, Peng M, Mirza A, Steinman RM, Nussenzweig MC. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature. 1995;375(6527):151–155.PubMedCrossRefGoogle Scholar
  47. 47.
    Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 2001;194(6):769–779.PubMedCrossRefGoogle Scholar
  48. 48.
    Engering AJ, Cella M, Fluitsma D, Brockhaus M, Hoefsmit EC, Lanzavecchia A, Pieters J. The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells. Euro J Immunol. 1997;27(9):2417–2425.CrossRefGoogle Scholar
  49. 49.
    Largent BL, Walton KM, Hoppe CA, Lee YC, Schnaar RL. Carbohydrate-specific adhesion of alveolar macrophages to mannose-derivatized surfaces. J Biol Chem. 1984;259(3):1764–1769.PubMedGoogle Scholar
  50. 50.
    Taylor ME, Bezouska K, Drickamer K. Contribution to ligand binding by multiple carbohydrate-recognition domains in the macrophage mannose receptor. J Biol Chem. 1992;267(3):1719–1726.PubMedGoogle Scholar
  51. 51.
    Tsuji T, Matsuzaki J, Kelly MP, Ramakrishna V, Vitale L, He LZ, Keler T, Odunsi K, Old LJ, Ritter G, Gnjatic S. 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 (Baltimore, Md : 1950). 2011;186(2):1218–1227.Google Scholar
  52. 52.
    Zehner M, Chasan AI, Schuette V, Embgenbroich M, Quast T, Kolanus W, Burgdorf S. Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation. Proc Nat Acad Sci USA. 2011;108(24):9933–9938.PubMedCrossRefGoogle Scholar
  53. 53.
    Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Burgdorf S, Saeland E, Kurts C, Unger WW, van Kooyk Y. Design of neo-glycoconjugates that target the mannose receptor and enhance TLR-independent cross-presentation and Th1 polarization. Euro J Immunol. 2011;41(4):916–925.CrossRefGoogle Scholar
  54. 54.
    Kerrigan AM, Brown GD. C-type lectins and phagocytosis. Immunobiology. 2009;214(7):562–575.PubMedCrossRefGoogle Scholar
  55. 55.
    Brown GD, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature. 2001;413(6851):36–37.PubMedCrossRefGoogle Scholar
  56. 56.
    Herre J, Marshall ASJ, Caron E, Edwards AD, Williams DL, Schweighoffer E, Tybulewicz V, Reis e Sousa C, Gordon S, Brown GD. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood. 2004;104(13):4038–4045.PubMedCrossRefGoogle Scholar
  57. 57.
    Weck MM, Appel S, Werth D, Sinzger C, Bringmann A, Grünebach F, Brossart P. hDectin-1 is involved in uptake and cross-presentation of cellular antigens. Blood. 2008;111(8):4264–4272.PubMedCrossRefGoogle Scholar
  58. 58.
    Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 2000;100(5):575–585.PubMedCrossRefGoogle Scholar
  59. 59.
    Zhang P, Snyder S, Feng P, Azadi P, Zhang S, Bulgheresi S, Sanderson KE, He J, Klena J, Chen T. Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting the DC-SIGN (CD209). J Immunol (Baltimore, Md : 1950). 2006;177(6):4002–4011.Google Scholar
  60. 60.
    Mitchell DA, Fadden AJ, Drickamer K. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem. 2001;276(31):28,939–28,945.CrossRefGoogle Scholar
  61. 61.
    Tacken PJ, Ginter W, Berod L, Cruz LJ, Joosten B, Sparwasser T, Figdor CG, Cambi A. Targeting DC-SIGN via its neck region leads to prolonged antigen residence in early endosomes, delayed lysosomal degradation and cross-presentation. Blood 2011;118(15):4111–4119.Google Scholar
  62. 62.
    Geijtenbeek TBH, Gringhuis SI. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol. 2010;9(7):465–479.CrossRefGoogle Scholar
  63. 63.
    Meyer-Wentrup F, Benitez-Ribas D, Tacken PJ, Punt CJA, Figdor CG, de Vries IJM, Adema GJ. Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production. Blood. 2008;111(8):4245–4253.PubMedCrossRefGoogle Scholar
  64. 64.
    Meyer-Wentrup F, Cambi A, Joosten B, Looman MW, de Vries IJM, Figdor CG, Adema GJ. DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production. J Leukoc Biol. 2009;85(3):518–525.PubMedCrossRefGoogle Scholar
  65. 65.
    Lambert AA, Gilbert C, Richard M, Beaulieu AD, Tremblay MJ. The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways. Blood. 2008;112(4):1299–1307.PubMedCrossRefGoogle Scholar
  66. 66.
    Klechevsky E, Flamar AL, Cao Y, Blanck JP, Liu M, O’Bar A, Agouna-Deciat O, Klucar P, Thompson-Snipes L, Zurawski S, Reiter Y, Palucka AK, Zurawski G, Banchereau J. Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR. Blood. 2010;116(10):1685–1697.PubMedCrossRefGoogle Scholar
  67. 67.
    Bates EE, Fournier N, Garcia E, Valladeau J, Durand I, Pin JJ, Zurawski SM, Patel S, Abrams JS, Lebecque S, Garrone P, Saeland S. APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. J Immunol (Baltimore, Md : 1950). 1999;163(4):1973–1983.Google Scholar
  68. 68.
    Jin Y, Fuller L, Ciancio G, Burke GW, Tzakis AG, Ricordi C, Miller J, Esquenzai V. Antigen presentation and immune regulatory capacity of immature and mature-enriched antigen presenting (dendritic) cells derived from human bone marrow. Human Immunol. 2004;65(2):93–103.CrossRefGoogle Scholar
  69. 69.
    Butler M, Morel AS, Jordan WJ, Eren E, Hue S, Shrimpton RE, Ritter MA. Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205-DCL-1 fusion protein upon dendritic cell maturation. Immunology. 2007;120(3):362–371.PubMedCrossRefGoogle Scholar
  70. 70.
    Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Aït-Yahia S, Brière F, Zlotnik A, Lebecque S, Caux C. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med. 1998;188(2):373–386.PubMedCrossRefGoogle Scholar
  71. 71.
    Cao X, Zhang W, Wan T, He L, Chen T, Yuan Z, Ma S, Yu Y, Chen G. Molecular cloning and characterization of a novel CXC chemokine macrophage inflammatory protein-2 gamma chemoattractant for human neutrophils and dendritic cells. J Immunol (Baltimore, Md: 1950). 2000;165(5):2588–2595.Google Scholar
  72. 72.
    Power CA, Church DJ, Meyer A, Alouani S, Proudfoot AE, Clark-Lewis I, Sozzani S, Mantovani A, Wells TN. Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells. J Exp Med. 1997;186(6):825–835.PubMedCrossRefGoogle Scholar
  73. 73.
    Sato K, Kawasaki H, Nagayama H, Serizawa R, Ikeda J, Morimoto C, Yasunaga K, Yamaji N, Tadokoro K, Juji T, Takahashi TA. CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells. Blood. 1999;93(1):34–42.PubMedGoogle Scholar
  74. 74.
    Sato K, Kawasaki H, Nagayama H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Takahashi TA. TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J Immunol (Baltimore, Md : 1950). 2000;164(5):2285–2295.Google Scholar
  75. 75.
    Burgdorf S, Schölz C, Kautz A, Tampé R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008;9(5):558–566.PubMedCrossRefGoogle Scholar
  76. 76.
    De Filippo A, Binder RJ, Camisaschi C, Beretta V, Arienti F, Villa A, Della Mina P, Parmiani G, Rivoltini L, Castelli C. Human plasmacytoid dendritic cells interact with gp96 via CD91 and regulate inflammatory responses. J Immunol (Baltimore, Md : 1950). 2008;181(9):6525–6535.Google Scholar
  77. 77.
    Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj N. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998;188(7):1359–1368.PubMedCrossRefGoogle Scholar
  78. 78.
    Bajtay Z, Csomor E, Sándor N, Erdei A. Expression and role of Fc- and complement-receptors on human dendritic cells. Immunol Lett. 2006;104(1-2):46–52.PubMedCrossRefGoogle Scholar
  79. 79.
    Liu Y, Gao X, Masuda E, Redecha PB, Blank MC, Pricop L. Regulated expression of FcgammaR in human dendritic cells controls cross-presentation of antigen-antibody complexes. J Immunol (Baltimore, Md: 1950). 2006;177(12):8440–8447.Google Scholar
  80. 80.
    Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol. 2001;19:275–290.PubMedCrossRefGoogle Scholar
  81. 81.
    Saeki H, Moore AM, Brown MJ, Hwang ST. Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol (Baltimore, Md : 1950). 1999;162(5):2472–2475.Google Scholar
  82. 82.
    Patterson S, Donaghy H, Amjadi P, Gazzard B, Gotch F, Kelleher P. Human BDCA-1-positive blood dendritic cells differentiate into phenotypically distinct immature and mature populations in the absence of exogenous maturational stimuli: differentiation failure in HIV infection. J Immunol (Baltimore, Md : 1950). 2005;174(12):8200–8209.Google Scholar
  83. 83.
    Swanson JA, Hoppe AD. The coordination of signaling during Fc receptor-mediated phagocytosis. J Leukoc Biol. 2004;76(6):1093–1103.PubMedCrossRefGoogle Scholar
  84. 84.
    Bergtold A, Desai DD, Gavhane A, Clynes R. Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity. 2005;23(5):503–514.PubMedCrossRefGoogle Scholar
  85. 85.
    Zhu X, Zhao X, Burkholder WF, Gragerov A, Ogata CM, Gottesman ME, Hendrickson WA. Structural analysis of substrate binding by the molecular chaperone DnaK. Science (New York, NY). 1996;272(5268):1606–1614.CrossRefGoogle Scholar
  86. 86.
    Basu S, Binder RJ, Ramalingam T, Srivastava PK. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity. 2001;14(3):303–313.PubMedCrossRefGoogle Scholar
  87. 87.
    Chu CT, Pizzo SV. Receptor-mediated antigen delivery into macrophages. Complexing antigen to alpha 2-macroglobulin enhances presentation to T cells. J Immunol (Baltimore, Md: 1950). 1993;150(1):48–58.Google Scholar
  88. 88.
    Nishikawa M, Takemoto S, Takakura Y. Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm. 2008;354(1-2):23–27.PubMedCrossRefGoogle Scholar
  89. 89.
    Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol. 2000; 12(11):1539–1546.PubMedCrossRefGoogle Scholar
  90. 90.
    Belizaire R, Unanue ER. Targeting proteins to distinct subcellular compartments reveals unique requirements for MHC class I and II presentation. Proc Nat Acad Sci USA. 2009;106(41):17,463–17,468.CrossRefGoogle Scholar
  91. 91.
    Lutz MB, Rovere P, Kleijmeer MJ, Rescigno M, Assmann CU, Oorschot VM, Geuze HJ, Trucy J, Demandolx D, Davoust J, Ricciardi-Castagnoli P. Intracellular routes and selective retention of antigens in mildly acidic cathepsin D/lysosome-associated membrane protein-1/MHC class II-positive vesicles in immature dendritic cells. J Immunol (Baltimore, Md : 1950). 1997;159(8):3707–3716.Google Scholar
  92. 92.
    van Montfoort N, Camps MG, Khan S, Filippov DV, Weterings JJ, Griffith JM, Geuze HJ, van Hall T, Verbeek JS, Melief CJ, Ossendorp F. Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity. Proc Nat Acad Sci USA. 2009;106(16):6730–6735.PubMedCrossRefGoogle Scholar
  93. 93.
    Duclos S, Clavarino G, Rousserie G, Goyette G, Boulais J, Camossetto V, Gatti E, LaBoissière S, Pierre P, Desjardins M. The endosomal proteome of macrophage and dendritic cells. Proteomics. 2011;11(5):854–864.PubMedCrossRefGoogle Scholar
  94. 94.
    McCurley N, Mellman I. Monocyte-derived dendritic cells exhibit increased levels of lysosomal proteolysis as compared to other human dendritic cell populations. PloS one. 2010;5(8):e11,949.CrossRefGoogle Scholar
  95. 95.
    Savina A, Jancic C, Hugues S, Guermonprez P, Vargas P, Moura IC, Lennon-Duménil AM, Seabra MC, Raposo G, Amigorena S. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell. 2006;126(1):205–218.PubMedCrossRefGoogle Scholar
  96. 96.
    Baker K, Qiao SW, Kuo TT, Aveson VG, Platzer B, Andersen JT, Sandlie I, Chen Z, de Haar C, Lencer WI, Fiebiger E, Blumberg RS. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc Nat Acad Sci USA. 2011;108(24):9927–9932.PubMedCrossRefGoogle Scholar
  97. 97.
    Trombone APF, Silva CL, Lima KM, Oliver C, Jamur MC, Prescott AR, Coelho-Castelo AAM. Endocytosis of DNA-Hsp65 alters the pH of the late endosome/lysosome and interferes with antigen presentation. PloS one. 2007;2(9):e923.PubMedCrossRefGoogle Scholar
  98. 98.
    Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801–847.PubMedCrossRefGoogle Scholar
  99. 99.
    Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature. 1997;386(6624):463–471.PubMedCrossRefGoogle Scholar
  100. 100.
    Kloetzel PM, Ossendorp F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentation. Curr Opin Immunol. 2004;16(1):76–81.PubMedCrossRefGoogle Scholar
  101. 101.
    Garbi N, Hämmerling G, Tanaka S. Interaction of ERp57 and tapasin in the generation of MHC class I-peptide complexes. Curr Opin Immunol. 2007;19(1):99–105.PubMedCrossRefGoogle Scholar
  102. 102.
    Kukutsch NA, Rossner S, Austyn JM, Schuler G, Lutz MB. Formation and kinetics of MHC class I-ovalbumin peptide complexes on immature and mature murine dendritic cells. J Investig Dermatol. 2000;115(3):449–453.PubMedCrossRefGoogle Scholar
  103. 103.
    Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991–1045.PubMedCrossRefGoogle Scholar
  104. 104.
    Whiteside TL, Stanson J, Shurin MR, Ferrone S. Antigen-processing machinery in human dendritic cells: up-regulation by maturation and down-regulation by tumor cells. J Immunol (Baltimore, Md : 1950). 2004;173(3):1526–1534.Google Scholar
  105. 105.
    Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135–145.PubMedCrossRefGoogle Scholar
  106. 106.
    Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with toll-like receptor agonists and antagonists. Nat Med. 2007;13(5):552–559.PubMedCrossRefGoogle Scholar
  107. 107.
    Faure-André G, Vargas P, Yuseff MI, Heuzé M, Diaz J, Lankar D, Steri V, Manry J, Hugues S, Vascotto F, Boulanger J, Raposo G, Bono MR, Rosemblatt M, Piel M, Lennon-Duménil AM. Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. Science (New York, NY). 2008;322(5908):1705–1710.CrossRefGoogle Scholar
  108. 108.
    Groettrup M, Soza A, Kuckelkorn U, Kloetzel PM. Peptide antigen production by the proteasome: complexity provides efficiency. Immunol Today. 1996;17(9):429–435.PubMedCrossRefGoogle Scholar
  109. 109.
    Realini C, Dubiel W, Pratt G, Ferrell K, Rechsteiner M. Molecular cloning and expression of a gamma-interferon-inducible activator of the multicatalytic protease. J Biol Chem. 1994;269(32):20,727–20,732.Google Scholar
  110. 110.
    Siddiqui S, Alatery A, Kus A, Basta S. TLR engagement prior to virus infection influences MHC-I antigen presentation in an epitope-dependent manner as a result of nitric oxide release. J Leukoc Biol. 2011;89(3):457–468.PubMedCrossRefGoogle Scholar
  111. 111.
    Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 1997;91(4):521–530.PubMedCrossRefGoogle Scholar
  112. 112.
    Yanagihara S, Komura E, Nagafune J, Watarai H, Yamaguchi Y. EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation. J Immunol (Baltimore, Md : 1950). 1998;161(6):3096–3102.Google Scholar
  113. 113.
    Fanning SL, George TC, Feng D, Feldman SB, Megjugorac NJ, Izaguirre AG, Fitzgerald-Bocarsly P. Receptor cross-linking on human plasmacytoid dendritic cells leads to the regulation of IFN-alpha production. J Immunol (Baltimore, Md : 1950). 2006;177(9):5829–5839.Google Scholar
  114. 114.
    Venturi GM, Tu L, Kadono T, Khan AI, Fujimoto Y, Oshel P, Bock CB, Miller AS, Albrecht RM, Kubes P, Steeber DA, Tedder TF. Leukocyte migration is regulated by L-selectin endoproteolytic release. Immunity. 2003;19(5):713–724.PubMedCrossRefGoogle Scholar
  115. 115.
    Watts C, West MA, Zaru R. TLR signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol. 2010;22(1):124–130.PubMedCrossRefGoogle Scholar
  116. 116.
    Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. CD14 Controls the LPS-induced endocytosis of toll-like receptor 4. Cell. 2011;147(4):868–880.PubMedCrossRefGoogle Scholar
  117. 117.
    Husebye H, Halaas Ø, Stenmark H, Tunheim G, Sandanger Ø, Bogen B, Brech A, Latz E, Espevik T. Endocytic pathways regulate toll-like receptor 4 signaling and link innate and adaptive immunity. EMBO J. 2006;25(4):683–692.PubMedCrossRefGoogle Scholar
  118. 118.
    Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R. TRAM couples endocytosis of toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008;9(4):361–368.PubMedCrossRefGoogle Scholar
  119. 119.
    Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K. Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem Biophys Res Commun. 2008;368(1):94–99.PubMedCrossRefGoogle Scholar
  120. 120.
    Blander JM, Medzhitov R. On regulation of phagosome maturation and antigen presentation. Nat Immunol. 2006;7(10):1029–1035.PubMedCrossRefGoogle Scholar
  121. 121.
    Husebye H, Aune MH, Stenvik J, Samstad E, Skjeldal F, Halaas Ø, Nilsen NJ, Stenmark H, Latz E, Lien E, Mollnes TE, Bakke O, Espevik T. The Rab11a GTPase controls Toll-like receptor 4-induced activation of interferon regulatory factor-3 on phagosomes. Immunity. 2010;33(4):583–596.PubMedCrossRefGoogle Scholar
  122. 122.
    Palsson-McDermott EM, Doyle SL, McGettrick AF, Hardy M, Husebye H, Banahan K, Gong M, Golenbock D, Espevik T, O’Neill LAJ. TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway. Nat Immunol. 2009;10(6):579–586.PubMedCrossRefGoogle Scholar
  123. 123.
    Akazawa T, Ebihara T, Okuno M, Okuda Y, Shingai M, Tsujimura K, Takahashi T, Ikawa M, Okabe M, Inoue N, Okamoto-Tanaka M, Ishizaki H, Miyoshi J, Matsumoto M, Seya T. Antitumor NK activation induced by the toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Nat Acad Sci USA. 2007;104(1):252–257.PubMedCrossRefGoogle Scholar
  124. 124.
    Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature. 2008;456(7222):658–662.PubMedCrossRefGoogle Scholar
  125. 125.
    Nishiya T, Kajita E, Miwa S, Defranco AL. TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements. J Biol Chem. 2005;280(44):37,107–37,117.CrossRefGoogle Scholar
  126. 126.
    Park B, Brinkmann MM, Spooner E, Lee CC, Kim YM, Ploegh HL. Proteolytic cleavage in an endolysosomal compartment is required for activation of toll-like receptor 9. Nat Immunol. 2008;9(12):1407–1414.PubMedCrossRefGoogle Scholar
  127. 127.
    Häcker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 1998;17(21):6230–6240.PubMedCrossRefGoogle Scholar
  128. 128.
    Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H. Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science (New York, NY). 2008;319(5863):624–627.CrossRefGoogle Scholar
  129. 129.
    Jelinek I, Leonard JN, Price GE, Brown KN, Meyer-Manlapat A, Goldsmith PK, Wang Y, Venzon D, Epstein SL, Segal DM. TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J Immunol (Baltimore, Md : 1950). 2011;186(4):2422–2429.Google Scholar
  130. 130.
    Ermolaeva MA, Michallet MC, Papadopoulou N, Utermöhlen O, Kranidioti K, Kollias G, Tschopp J, Pasparakis M. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol. 2008;9(9):1037–1046.PubMedCrossRefGoogle Scholar
  131. 131.
    Pobezinskaya YL, Kim YS, Choksi S, Morgan MJ, Li T, Liu C, Liu Z. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent toll-like receptors. Nat Immunol. 2008;9(9):1047–1054.PubMedCrossRefGoogle Scholar
  132. 132.
    Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A. Selected toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol. 2005;6(8):769–776.PubMedCrossRefGoogle Scholar
  133. 133.
    Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Reis e Sousa C. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005;22(4):507–517.PubMedCrossRefGoogle Scholar
  134. 134.
    Blander JM, Medzhitov R. Regulation of phagosome maturation by signals from toll-like receptors. Science (New York, NY). 2004;304(5673):1014–1018.CrossRefGoogle Scholar
  135. 135.
    West MA, Wallin RPA, Matthews SP, Svensson HG, Zaru R, Ljunggren HG, Prescott AR, Watts C. Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science (New York, NY). 2004;305(5687):1153–1157.CrossRefGoogle Scholar
  136. 136.
    Lakadamyali M, Rust MJ, Zhuang X. Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell. 2006;124(5):997–1009.PubMedCrossRefGoogle Scholar
  137. 137.
    Carbone FR, Bevan MJ. Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. J Exp Med. 1990;171(2):377–387.PubMedCrossRefGoogle Scholar
  138. 138.
    Gagnon E, Duclos S, Rondeau C, Chevet E, Cameron PH, Steele-Mortimer O, Paiement J, Bergeron JJM, Desjardins M. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell. 2002;110(1):119–131.PubMedCrossRefGoogle Scholar
  139. 139.
    Jancic C, Savina A, Wasmeier C, Tolmachova T, El-Benna J, Dang PMC, Pascolo S, Gougerot-Pocidalo MA, Raposo G, Seabra MC, Amigorena S. Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes. Nat Cell Biol. 2007;9(4):367–378.PubMedCrossRefGoogle Scholar
  140. 140.
    Houde M, Bertholet S, Gagnon E, Brunet S, Goyette G, Laplante A, Princiotta MF, Thibault P, Sacks D, Desjardins M. Phagosomes are competent organelles for antigen cross-presentation. Nature. 2003;425(6956):402–406.PubMedCrossRefGoogle Scholar
  141. 141.
    Ackerman AL, Kyritsis C, Tampé R, Cresswell P. Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells. Nat Immunol. 2005;6(1):107–113.PubMedCrossRefGoogle Scholar
  142. 142.
    Guermonprez P, Saveanu L, Kleijmeer M, Davoust J, van Endert P, Amigorena S. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature. 2003;425(6956):397–402.PubMedCrossRefGoogle Scholar
  143. 143.
    Giodini A, Cresswell P. Hsp90-mediated cytosolic refolding of exogenous proteins internalized by dendritic cells. EMBO J. 2008;27(1):201–211.PubMedCrossRefGoogle Scholar
  144. 144.
    Bertholet S, Goldszmid R, Morrot A, Debrabant A, Afrin F, Collazo-Custodio C, Houde M, Desjardins M, Sher A, Sacks D. Leishmania antigens are presented to CD8+ T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo. J Immunol (Baltimore, Md : 1950). 2006;177(6):3525–3533.Google Scholar
  145. 145.
    Di Pucchio T, Chatterjee B, Smed-Sörensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008;9(5):551–557.PubMedCrossRefGoogle Scholar
  146. 146.
    Basha G, Lizée G, Reinicke AT, Seipp RP, Omilusik KD, Jefferies WA. MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen loading in dendritic cells. PloS one. 2008;3(9):e3247.PubMedCrossRefGoogle Scholar
  147. 147.
    Zou L, Zhou J, Zhang J, Li J, Liu N, Chai L, Li N, Liu T, Li L, Xie Z, Liu H, Wan Y, Wu Y. The GTPase Rab3b/3c-positive recycling vesicles are involved in cross-presentation in dendritic cells. Proc Nat Acad Sci USA. 2009;106(37):15,801–15,806.CrossRefGoogle Scholar
  148. 148.
    Firat E, Saveanu L, Aichele P, Staeheli P, Huai J, Gaedicke S, Nil A, Besin G, Kanzler B, van Endert P, Niedermann G. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. J Immunol (Baltimore, Md : 1950). 2007;178(4):2241–2248.Google Scholar
  149. 149.
    Lake RA, Robinson BWS. Immunotherapy and chemotherapy–a practical partnership. Nat Rev Cancer. 2005;5(5):397–405.PubMedCrossRefGoogle Scholar
  150. 150.
    Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4(3):328–332.PubMedCrossRefGoogle Scholar
  151. 151.
    Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(11):3520–3526.CrossRefGoogle Scholar
  152. 152.
    Silk KM, Silk JD, Ichiryu N, Davies TJ, Nolan KF, Leishman AJ, Carpenter L, Watt SM, Cerundolo V, Fairchild PJ. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141+XCR1+ dendritic cells. Gene Ther. 2011. doi: 10.1038/gt.2011.177.
  153. 153.
    Huang XL, Fan Z, Zheng L, Borowski L, Li H, Thomas EK, Hildebrand WH, Zhao XQ, Rinaldo CR Jr. Priming of human immunodeficiency virus type 1 (HIV1)–specific CD8 +T cell responses by dendritic cells loaded with HIV1 proteins. J Infect Dis. 2003;187(2):315–319.PubMedCrossRefGoogle Scholar
  154. 154.
    Lu W, Arraes LC, Ferreira WT, Andrieu JM. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med. 2004;10(12):1359–1365.PubMedCrossRefGoogle Scholar
  155. 155.
    Dubsky P, Saito H, Leogier M, Dantin C, Connolly JE, Banchereau J, Palucka AK. IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. Euro J Immunol. 2007;37(6):1678–1690.CrossRefGoogle Scholar
  156. 156.
    Mohamadzadeh M, Berard F, Essert G, Chalouni C, Pulendran B, Davoust J, Bridges G, Palucka AK, Banchereau J. Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. J Exp Med. 2001;194(7):1013–1020.PubMedCrossRefGoogle Scholar
  157. 157.
    Paquette RL, Hsu NC, Kiertscher SM, Park AN, Tran L, Roth MD, Glaspy JA. Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J Leukoc Biol. 1998;64(3):358–367.PubMedGoogle Scholar
  158. 158.
    Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994;180(1):83–93.PubMedCrossRefGoogle Scholar
  159. 159.
    Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U, Murphy KM, Schreiber RD. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208(10):1989–2003.PubMedCrossRefGoogle Scholar
  160. 160.
    Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, Murphy KM, Gajewski TF. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8alpha+ dendritic cells. J Exp Med. 2011;208(10):2005–2016.PubMedCrossRefGoogle Scholar
  161. 161.
    Le Bon A, Etchart N, Rossmann C, Ashton M, Hou S, Gewert D, Borrow P, Tough DF. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol. 2003;4(10):1009–1015.PubMedCrossRefGoogle Scholar
  162. 162.
    Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, Van Dyke T, Pulendran B. Cutting edge: different toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol (Baltimore, Md : 1950). 2003;171(10):4984–4989.Google Scholar
  163. 163.
    Dalpke AH, Schäfer MKH, Frey M, Zimmermann S, Tebbe J, Weihe E, Heeg K. Immunostimulatory CpG-DNA activates murine microglia. J Immunol (Baltimore, Md : 1950). 2002;168(10):4854–4863.Google Scholar
  164. 164.
    Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.PubMedCrossRefGoogle Scholar
  165. 165.
    Loré K, Betts MR, Brenchley JM, Kuruppu J, Khojasteh S, Perfetto S, Roederer M, Seder RA, Koup RA. Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J Immunol (Baltimore, Md : 1950). 2003;171(8):4320–4328.Google Scholar
  166. 166.
    Pulendran B, Kumar P, Cutler CW, Mohamadzadeh M, Van Dyke T, Banchereau J. Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. J Immunol (Baltimore, Md : 1950). 2001;167(9):5067–5076.Google Scholar
  167. 167.
    Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee HW, Park CG, Steinman RM, Nussenzweig MC. Differential antigen processing by dendritic cell subsets in vivo. Science (New York, NY). 2007;315(5808):107–111.CrossRefGoogle Scholar
  168. 168.
    Crozat K, Guiton R, Contreras V, Feuillet V, Dutertre CA, Ventre E, Vu Manh TP, Baranek T, Storset AK, Marvel J, Boudinot P, Hosmalin A, Schwartz-Cornil I, Dalod M. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J Exp Med. 2010;207(6):1283–1292.PubMedCrossRefGoogle Scholar
  169. 169.
    Lauterbach H, Bathke B, Gilles S, Traidl-Hoffmann C, Luber CA, Fejer G, Freudenberg MA, Davey GM, Vremec D, Kallies A, Wu L, Shortman K, Chaplin P, Suter M, O’Keeffe M, Hochrein H. Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med. 2010;207(12):2703–2717.PubMedCrossRefGoogle Scholar
  170. 170.
    Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, Keller AM, Joffre O, Zelenay S, Nye E, Le Moine A, Faure F, Donckier V, Sancho D, Cerundolo V, Bonnet D, Reis e Sousa C. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J Exp Med. 2010;207(6):1261–1271.PubMedCrossRefGoogle Scholar
  171. 171.
    Bozzacco L, Trumpfheller C, Siegal FP, Mehandru S, Markowitz M, Carrington M, Nussenzweig MC, Piperno AG, Steinman RM. 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 Nat Acad Sci USA. 2007;104(4):1289–1294.PubMedCrossRefGoogle Scholar
  172. 172.
    Bozzacco L, Trumpfheller C, Huang Y, Longhi MP, Shimeliovich I, Schauer JD, Park CG, Steinman RM. HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Euro J Immunol. 2010;40(1):36–46.CrossRefGoogle Scholar
  173. 173.
    Ni L, Gayet I, Zurawski S, Duluc D, Flamar AL, Li XH, O’Bar A, Clayton S, Palucka AK, Zurawski G, Banchereau J, Oh S. Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses. J Immunol (Baltimore, Md : 1950). 2010;185(6):3504–3513.Google Scholar
  174. 174.
    Gil M, Bieniasz M, Wierzbicki A, Bambach BJ, Rokita H, Kozbor D. Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic cells to prime specific CD8+ T cell responses in tumor-bearing mice. J Immunol (Baltimore, Md : 1950). 2009;183(10):6808–6818.Google Scholar
  175. 175.
    Wallace PK, Tsang KY, Goldstein J, Correale P, Jarry TM, Schlom J, Guyre PM, Ernstoff MS, Fanger MW. Exogenous antigen targeted to FcgammaRI on myeloid cells is presented in association with MHC class I. J Immunol Methods. 2001;248(1-2):183–194.PubMedCrossRefGoogle Scholar
  176. 176.
    Ye L, Zeng R, Bai Y, Roopenian DC, Zhu X. Efficient mucosal vaccination mediated by the neonatal Fc receptor. Nat Biotechnol. 2011;29(2):158–163.PubMedCrossRefGoogle Scholar
  177. 177.
    He LZ, Crocker A, Lee J, Mendoza-Ramirez J, Wang XT, Vitale LA, O’Neill T, Petromilli C, Zhang HF, Lopez J, Rohrer D, Keler T, Clynes R. Antigenic targeting of the human mannose receptor induces tumor immunity. J Immunol (Baltimore, Md : 1950). 2007;178(10):6259–6267.Google Scholar
  178. 178.
    Ramakrishna V, Vasilakos JP, Tario JD, Berger MA, Wallace PK, Keler T. Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells. J Trans Med. 2007;5:5.CrossRefGoogle Scholar
  179. 179.
    Altmann F, Staudacher E, Wilson IB, März L. Insect cells as hosts for the expression of recombinant glycoproteins. Glycoconj J. 1999;16(2):109–123.PubMedCrossRefGoogle Scholar
  180. 180.
    Betting DJ, Mu XY, Kafi K, McDonnel D, Rosas F, Gold DP, Timmerman JM. Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells. Vaccine. 2009;27(2):250–259.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Program in Translational ImmunologySingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)SingaporeSingapore

Personalised recommendations