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Letters to Nature

Nature 425, 397-402 (25 September 2003) | doi:10.1038/nature01911; Received 17 March 2003; Accepted 10 July 2003

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

Pierre Guermonprez1,5, Loredana Saveanu2,5, Monique Kleijmeer3, Jean Davoust4, Peter van Endert2 & Sebastian Amigorena1

  1. INSERM U520, Institut Curie, 26 rue d'Ulm, 75005 Paris, France
  2. INSERM U580, Institut Necker, 161 rue de Sèvres, 75015 Paris, France
  3. Department of Cell Biology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
  4. CNRS UMR8115, Genethon, 1 bis rue de l'Internationnale, 91002 Cedex 02, Evry, France
  5. These authors contributed equally to this work

Correspondence to: Sebastian Amigorena1 Email: sebastian.amigorena@curie.fr

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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.