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Damage-Associated Molecular Patterns in Human Diseases pp 723–748Cite as

Antigen Uptake, Processing, and Presentation by Dendritic Cells

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Abstract

In this chapter, the major mechanisms of antigen uptake, processing, and presentation by antigen-presenting cells, in particular dendritic cells, are compendiously explored. In the course of these processes, immature dendritic cells mature into immunostimulatory cells able to activate CD4+ and CD8+ T cells. Initial uptake of exogenous antigens is provided by mainly three phagocytic pathways, (1) receptor-mediated endocytosis, (2) phagocytosis, and (3) macropinocytosis. Engulfed exogenous antigens are prepared for further processing and presentation. By contrast, host-derived endogenous antigens are channelled for further processing and presentation via the cell-intrinsic machinery of autophagy. Depending on exogenous or endogenous sources, distinct pathways are involved in processing and presentation of antigenic peptides loaded on MHC molecules. Exogenous antigenic proteins are processed to peptides in endolysosomal compartments to be loaded on MHC-II molecules biosynthesized in the endoplasmic reticulum. The peptide/MHC-II complexes leave the endosomal antigen-processing compartments to be transported to and inserted into the plasma membrane for T cell recognition by CD4+ T cells. However, exogenous antigenic proteins, when degraded to peptides by the immunoproteasome or processed in endocytic compartments, can also be loaded on MHC-I molecules to be cross-presented to CD8+ T cells. On the other hand, endogenous cytosolic antigenic proteins are processed to peptides in complex proteasome-dependent and proteasome-independent pathways to be loaded on MHC-I molecules in the endoplasmic reticulum. The peptide/MHC-I complexes then leave within vesicles for transport through the Golgi apparatus to become inserted into plasma membrane for T cell recognition by CD8+ T cells. However, endogenous antigenic proteins can also be loaded on MHC-II molecules via involvement of autophagic processes to be cross-presented to CD4+ T cells. Notably, a potentially crucial role of DAMPs in the scenario of both direct antigen presentation and cross-presentation is finally discussed.

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References

  1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52. https://doi.org/10.1038/32588.

    Article  CAS  Google Scholar 

  2. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767–811. https://doi.org/10.1146/annurev.immunol.18.1.767.

    Article  CAS  Google Scholar 

  3. Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med. 2000;191:411–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10662786

    Article  CAS  Google Scholar 

  4. Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A. 2002;99:351–8. https://doi.org/10.1073/pnas.231606698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Steinman RM, Hemmi H. Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol. 2006;311:17–58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17048704

    CAS  PubMed  Google Scholar 

  6. Idoyaga J, Steinman RM. SnapShot: dendritic cells. Cell. 2011;146:660–660.e2. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0092867411008932

    Article  CAS  Google Scholar 

  7. Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22136168

    Article  CAS  Google Scholar 

  8. Steinman RM, Idoyaga J. Features of the dendritic cell lineage. Immunol Rev. 2010;234:5–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20193008

    Article  CAS  Google Scholar 

  9. Mellman I. Dendritic cells: master regulators of the immune response. Cancer Immunol Res. 2013;1:145–9. https://doi.org/10.1158/2326-6066.CIR-13-0102.

    Article  CAS  PubMed  Google Scholar 

  10. Raghavan M, Wijeyesakere SJ, Peters LR, Del Cid N. Calreticulin in the immune system: ins and outs. Trends Immunol. 2013;34:13–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22959412

    Article  CAS  Google Scholar 

  11. Sukkurwala AQ, Martins I, Wang Y, Schlemmer F, Ruckenstuhl C, Durchschlag M, et al. Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8. Cell Death Differ. 2014;21:59–68. https://doi.org/10.1038/cdd.2013.73.

    Article  CAS  PubMed  Google Scholar 

  12. Villadangos JA, Schnorrer P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol. 2007;7:543–55. https://doi.org/10.1038/nri2103.

    Article  CAS  PubMed  Google Scholar 

  13. Taylor MJ, Perrais D, Merrifield CJ. A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLoS Biol. 2011;9:e1000604. Available from: http://dx.plos.org/10.1371/journal.pbio.1000604

    Article  CAS  Google Scholar 

  14. Godlee C, Kaksonen M. Review series: From uncertain beginnings: initiation mechanisms of clathrin-mediated endocytosis. J Cell Biol. 2013;203:717–25. https://doi.org/10.1083/jcb.201307100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Robinson MS. Forty years of clathrin-coated vesicles. Traffic. 2015;16:1210–38. https://doi.org/10.1111/tra.12335.

    Article  CAS  PubMed  Google Scholar 

  16. Burgdorf S, Kurts C. Endocytosis mechanisms and the cell biology of antigen presentation. Curr Opin Immunol. 2008;20:89–95. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0952791507002087

    Article  CAS  Google Scholar 

  17. Liu Z, Roche PA. Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells. Front Physiol. 2015;6:1. Available from: http://journal.frontiersin.org/article/10.3389/fphys.2015.00001/abstract

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Stuart LM, Ezekowitz RAB. Phagocytosis. Immunity. 2005;22:539–50. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761305001342

    Article  CAS  Google Scholar 

  19. Mantegazza AR, Zajac AL, Twelvetrees A, Holzbaur ELF, Amigorena S, Marks MS. TLR-dependent phagosome tubulation in dendritic cells promotes phagosome cross-talk to optimize MHC-II antigen presentation. Proc Natl Acad Sci. 2014;111:15508–13. https://doi.org/10.1073/pnas.1412998111.

    Article  CAS  PubMed  Google Scholar 

  20. Szondy Z, Garabuczi Ã, Joós G, Tsay GJ, Sarang Z. Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. Front Immunol. 2014;5:354. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2014.00354/abstract

    Article  Google Scholar 

  21. Biermann MHC, Veissi S, Maueröder C, Chaurio R, Berens C, Herrmann M, et al. The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: dendritic cells as potential targets. Expert Rev Clin Immunol. 2014;10:1151–64. https://doi.org/10.1586/1744666X.2014.944162.

    Article  CAS  PubMed  Google Scholar 

  22. Lim JP, Gleeson PA. Macropinocytosis: an endocytic pathway for internalising large gulps. Immunol Cell Biol. 2011;89:836–43. https://doi.org/10.1038/icb.2011.20.

    Article  CAS  PubMed  Google Scholar 

  23. Swanson JA, Watts C. Macropinocytosis. Trends Cell Biol. 1995;5:424–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14732047

    Article  CAS  Google Scholar 

  24. Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389–400. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7629501

    Article  CAS  Google Scholar 

  25. West MA, Wallin RPA, Matthews SP, Svensson HG, Zaru R, Ljunggren H-G, et al. Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science. 2004;305:1153–7. https://doi.org/10.1126/science.1099153.

    Article  CAS  PubMed  Google Scholar 

  26. Blander JM, Medzhitov R. On regulation of phagosome maturation and antigen presentation. Nat Immunol. 2006;7:1029–35. https://doi.org/10.1038/ni1006-1029.

    Article  CAS  PubMed  Google Scholar 

  27. Münz C. Antigen processing for MHC class II presentation via autophagy. Front Immunol. 2012;3:9. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2012.00009/abstract

    Article  Google Scholar 

  28. Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31:443–73. https://doi.org/10.1146/annurev-immunol-032712-095910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15:203–16. https://doi.org/10.1038/nri3818.

    Article  CAS  PubMed  Google Scholar 

  30. Duraes FV, Niven J, Dubrot J, Hugues S, Gannagé M. Macroautophagy in endogenous processing of self- and pathogen-derived antigens for MHC class II presentation. Front Immunol. 2015;6:459. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00459/abstract

    Article  Google Scholar 

  31. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, et al. Microautophagy of cytosolic proteins by late endosomes. Dev Cell. 2011;20:131–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1534580710005848

    Article  CAS  Google Scholar 

  32. Leung CSK. Endogenous antigen presentation of MHC class II epitopes through non-autophagic pathways. Front Immunol. 2015;6:464. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00464/abstract

    Article  Google Scholar 

  33. Segura E, Villadangos JA. Antigen presentation by dendritic cells in vivo. Curr Opin Immunol. 2009;21:105–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19342210

    Article  CAS  Google Scholar 

  34. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12:557–69. https://doi.org/10.1038/nri3254.

    Article  CAS  Google Scholar 

  35. Trowsdale J, Knight JC. Major histocompatibility complex genomics and human disease. Annu Rev Genomics Hum Genet. 2013;14:301–23. https://doi.org/10.1146/annurev-genom-091212-153455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Janeway CA, Travers P, Walport M. In: Kenneth M, editor. Immunobiology. 8th ed. New York: Garland, Science, Taylor and Francis Group; LLC; 2012.

    Google Scholar 

  37. Pratheek BM, Nayak TK, Sahoo SS, Mohanty PK, Chattopadhyay S, Chakraborty NG, et al. Mammalian non-classical major histocompatibility complex I and its receptors: important contexts of gene, evolution, and immunity. Indian J Hum Genet. 2014;20:129–41. Available from: http://www.ijhg.com/text.asp?2014/20/2/129/142855

    Article  CAS  Google Scholar 

  38. Saftig P, Klumperman J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol. 2009;10:623–35. https://doi.org/10.1038/nrm2745.

    Article  CAS  PubMed  Google Scholar 

  39. Jovic M, Sharma M, Rahajeng J, Caplan S. The early endosome: a busy sorting station for proteins at the crossroads. Histol Histopathol. 2010;25:99–112. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19924646

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Huotari J, Helenius A. Endosome maturation. EMBO J. 2011;30:3481–500. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21878991

    Article  CAS  Google Scholar 

  41. Stern LJ, Potolicchio I, Santambrogio L. MHC class II compartment subtypes: structure and function. Curr Opin Immunol. 2006;18:64–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0952791505001986

    Article  CAS  Google Scholar 

  42. Watts C. The exogenous pathway for antigen presentation on major histocompatibility complex class II and CD1 molecules. Nat Immunol. 2004;5:685–92. Available from: http://www.nature.com/doifinder/10.1038/ni1088

    Article  CAS  Google Scholar 

  43. Maupin-Furlow J. Proteasomes and protein conjugation across domains of life. Nat Rev Microbiol. 2011;10:100–11. https://doi.org/10.1038/nrmicro2696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vigneron N, Van den Eynde BJ. Proteasome subtypes and regulators in the processing of antigenic peptides presented by class I molecules of the major histocompatibility complex. Biomolecules. 2014;4:994–1025. Available from: http://www.mdpi.com/2218-273X/4/4/994/

    Article  Google Scholar 

  45. Leone P, Shin E-C, Perosa F, Vacca A, Dammacco F, Racanelli V. MHC class I antigen processing and presenting machinery: organization, function, and defects in tumor cells. J Natl Cancer Inst. 2013;105:1172–87. https://doi.org/10.1093/jnci/djt184.

    Article  CAS  PubMed  Google Scholar 

  46. Trombetta ES, Mellman I. Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol. 2005;23:975–1028. https://doi.org/10.1146/annurev.immunol.22.012703.104538.

    Article  CAS  PubMed  Google Scholar 

  47. 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. 2007;316:612–6. https://doi.org/10.1126/science.1137971.

    Article  CAS  PubMed  Google Scholar 

  48. Eggensperger S, Tampé R. The transporter associated with antigen processing: a key player in adaptive immunity. Biol Chem. 2015;396:1059–72. Available from: http://www.degruyter.com/view/j/bchm.2015.396.issue-9-10/hsz-2014-0320/hsz-2014-0320.xml

    Article  CAS  Google Scholar 

  49. Roelse J, Grommé M, Momburg F, Hämmerling G, Neefjes J. Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J Exp Med. 1994;180:1591–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7964447

    Article  CAS  Google Scholar 

  50. Teague RM, Greenberg PD, Fowler C, Huang MZ, Tan X, Morimoto J, et al. Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor. Immunity. 2008;28:662–74. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761308001271

    Article  CAS  Google Scholar 

  51. Burgdorf S, Schölz C, Kautz A, Tampé R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008;9:558–66. https://doi.org/10.1038/ni.1601.

    Article  CAS  PubMed  Google Scholar 

  52. Nair-Gupta P, Blander JM. An updated view of the intracellular mechanisms regulating cross-presentation. Front Immunol. 2013;4:401. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2013.00401/abstract

    Article  Google Scholar 

  53. Nair-Gupta P, Baccarini A, Tung N, Seyffer F, Florey O, Huang Y, et al. TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell. 2014;158:506–21. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0092867414008010

    Article  CAS  Google Scholar 

  54. Fehres CM, Unger WWJ, Garcia-Vallejo JJ, van Kooyk Y. Understanding the biology of antigen cross-presentation for the design of vaccines against cancer. Front Immunol. 2014;5:149. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2014.00149/abstract

    Article  Google Scholar 

  55. Cruz FM, Colbert JD, Merino E, Kriegsman BA, Rock KL. The biology and underlying mechanisms of cross-presentation of exogenous antigens on MHC-I molecules. Annu Rev Immunol. 2017;35:149–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28125356

    Article  CAS  Google Scholar 

  56. Merzougui N, Kratzer R, Saveanu L, van Endert P. A proteasome-dependent, TAP-independent pathway for cross-presentation of phagocytosed antigen. EMBO Rep. 2011;12:1257–64. https://doi.org/10.1038/embor.2011.203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Powell BS, Andrianov AK, Fusco PC. Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes. Clin Exp Vaccine Res. 2015;4:23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25648619

    Article  CAS  Google Scholar 

  58. Salimu J, Spary LK, Al-Taei S, Clayton A, Mason MD, Staffurth J, et al. Cross-presentation of the Oncofetal tumor antigen 5T4 from irradiated prostate cancer cells – a key role for heat-shock protein 70 and receptor CD91. Cancer Immunol Res. 2015;3:678–88. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25678582

    Article  CAS  Google Scholar 

  59. Fehres CM, Bruijns SCM, Sotthewes BN, Kalay H, Schaffer L, Head SR, et al. Phenotypic and functional properties of human steady state CD14+ and CD1a+ antigen presenting cells and epidermal langerhans cells. PLoS One. 2015;10:e0143519. https://doi.org/10.1371/journal.pone.0143519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Schnurr M, Duewell P. Induction of immunogenic cell death by targeting RIG-I-like helicases in pancreatic cancer. Oncoimmunology. 2014;3:e955687. https://doi.org/10.4161/21624011.2014.955687.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Crotzer VL, Blum JS. Autophagy and adaptive immunity. Immunology. 2010;131:no-no. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20586810

    Article  Google Scholar 

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  1. University of Strasbourg, Molecular ImmunoRheumatology, Laboratory of Excellence Transplantex, Strasbourg, France

    Walter Gottlieb Land

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Land, W.G. (2018). Antigen Uptake, Processing, and Presentation by Dendritic Cells. In: Damage-Associated Molecular Patterns in Human Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-78655-1_31

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  • DOI: https://doi.org/10.1007/978-3-319-78655-1_31

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