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

Nature volume 425, pages 397–402 (2003)Cite this article

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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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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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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