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ER–phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells

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Abstract

Induction of cytotoxic T-cell immunity requires the phagocytosis of pathogens, virus-infected or dead tumour cells by dendritic cells1. Peptides derived from phagocytosed antigens are then presented to CD8+ T lymphocytes on major histocompatibility complex (MHC) class I molecules, a process called “cross-presentation”2,3. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4,5,6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57)7. Here we show that soon after or during formation, phagosomes fuse with the ER. After antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. Therefore, cross-presentation in dendritic cells occurs in a specialized, self-sufficient, ER–phagosome mix compartment.

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Figure 1: Rapid recruitment of ER at the early stages of phagosome biogenesis in immature dendritic cells.
Figure 2: TAP is recruited in early phagosomes.
Figure 3: Early peptide loading in phagosomes during cross-presentation.
Figure 4: In vitro reconstitution of TAP-mediated peptide transport and loading on MHC class I in purified phagosomes.

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References

  1. Guermonprez, P., Valladeau, J., Zitvogel, L. & Amigorena, S. Antigen Presentation and T Cell Stimulation by Dendritic Cells. Annu. Rev. Immunol. 20, 620–667 (2002)

    Article  Google Scholar 

  2. Heath, W. R. & Carbone, F. R. Cross-presentation, dendritic cells, tolerance and immunity. Annu. Rev. Immunol. 19, 47–64 (2001)

    Article  CAS  Google Scholar 

  3. Yewdell, J. W., Norbury, C. C. & Bennink, J. R. Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: implications for generating CD8 + T cell responses to infectious agents, tumors, transplants, and vaccines. Adv. Immunol. 73, 1–77 (1999)

    Article  CAS  Google Scholar 

  4. Kovacsovics-Bankowski, M. & Rock, K. L. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science 267, 243–246 (1995)

    Article  ADS  CAS  Google Scholar 

  5. Norbury, C. C., Chambers, B. J., Prescott, A. R., Ljunggren, H. G. & Watts, C. Constitutive macropinocytosis allows TAP-dependent major histocompatibility complex class I presentation of exogenous soluble antigen by bone marrow-derived dendritic cells. Eur. J. Immunol. 27, 280–288 (1997)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Cresswell, P., Bangia, N., Dick, T. & Diedrich, G. The nature of the MHC class I peptide loading complex. Immunol. Rev. 172, 21–28 (1999)

    Article  CAS  Google Scholar 

  8. Gagnon, E. et al. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 110, 119–131 (2002)

    Article  CAS  Google Scholar 

  9. Ramachandra, L., Sramkoski, R. M., Canaday, D. H., Boom, W. H. & Harding, C. V. Flow analysis of MHC molecules and other membrane proteins in isolated phagosomes. J. Immunol. Methods 213, 53–71 (1998)

    Article  CAS  Google Scholar 

  10. Griffiths, G., Quinn, P. & Warren, G. Dissection of the Golgi complex. I. Monensin inhibits the transport of viral membrane proteins from medial to trans Golgi cisternae in baby hamster kidney cells infected with Semliki Forest virus. J. Cell Biol. 96, 835–850 (1983)

    Article  CAS  Google Scholar 

  11. Porgador, A., Yewdell, J. W., Deng, Y., Bennink, J. R. & Germain, R. N. Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. Immunity 6, 715–726 (1997)

    Article  CAS  Google Scholar 

  12. Lemonnier, F. A. The utility of H-2 class I knockout mice. Virus Res. 82, 87–90 (2002)

    Article  CAS  Google Scholar 

  13. Rock, K. L., York, I. A., Saric, T. & Goldberg, A. L. Protein degradation and the generation of MHC class I-presented peptides. Adv. Immunol. 80, 1–70 (2002)

    Article  CAS  Google Scholar 

  14. Reits, E. et al. Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity 18, 97–108 (2003)

    Article  CAS  Google Scholar 

  15. Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17–27 (1994)

    Article  CAS  Google Scholar 

  16. Winzler, C. et al. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med. 185, 317–328 (1997)

    Article  CAS  Google Scholar 

  17. Thery, C. et al. Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J. Cell Biol. 147, 599–610 (1999)

    Article  CAS  Google Scholar 

  18. Desjardins, M., Huber, L. A., Parton, R. G. & Griffiths, G. Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus. J. Cell Biol. 124, 677–688 (1994)

    Article  CAS  Google Scholar 

  19. Daniel, S., Caillat-Zucman, S., Hammer, J., Bach, J. F. & van Endert, P. M. Absence of functional relevance of human transporter associated with antigen processing polymorphism for peptide selection. J. Immunol. 159, 2350–2357 (1997)

    CAS  PubMed  Google Scholar 

  20. Karttunen, J., Sanderson, S. & Shastri, N. Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens. Proc. Natl Acad. Sci. USA 89, 6020–6024 (1992)

    Article  ADS  CAS  Google Scholar 

  21. Raposo, G., Kleijmeer, M. J., Posthuma, G., Slot, J. W. & Geuze, H. J. in Handbook of Experimental Immunology 5th edn, Ch. 208, 1–11 (Elsevier, Cambridge, MA, 1997)

    Google Scholar 

  22. Houde, M. et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 425, 402–406 (2003)

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We want to thank S. Hugues for help with the OT-1 effector cells, J. Griffith for technical assistance and A. Lennon-Dusmenil for critical reading of the manuscript. P.G. is a Fellow of the ARC and CNRS. This work was supported by the Institut Curie, the INSERM and the Ligue de Contre le Cancer.

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Author notes

  1. Pierre Guermonprez and Loredana Saveanu: These authors contributed equally to this work

Authors and Affiliations

  1. INSERM U520, Institut Curie, 26 rue d'Ulm, 75005, Paris, France

    Pierre Guermonprez & Sebastian Amigorena

  2. INSERM U580, Institut Necker, 161 rue de Sèvres, 75015, Paris, France

    Loredana Saveanu & Peter van Endert

  3. Department of Cell Biology, UMC Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Monique Kleijmeer

  4. CNRS UMR8115, Genethon, 1 bis rue de l'Internationnale, 91002 Cedex 02, Evry, France

    Jean Davoust

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  1. Pierre Guermonprez
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  2. Loredana Saveanu
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  3. Monique Kleijmeer
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  4. Jean Davoust
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  5. Peter van Endert
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  6. Sebastian Amigorena
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Correspondence to Sebastian Amigorena.

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Guermonprez, P., Saveanu, L., Kleijmeer, M. et al. ER–phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425, 397–402 (2003). https://doi.org/10.1038/nature01911

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