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Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells

Nature Cell Biology volume 1, pages 362–368 (1999)Cite this article

Abstract

In order for cytotoxic T cells to initiate immune responses, peptides derived from internalized antigens must be presented to the cytotoxic T cells on major histocompatibility complex (MHC) class I molecules. Here we show that dendritic cells, the only antigen-presenting cells that initiate immune responses efficiently, have developed a unique membrane transport pathway linking the lumen of endocytic compartments and the cytosol. Endosome-to-cytosol transport is restricted to dendritic cells, specific to internalized antigens and selective for the size of the transported molecules. Thus, in dendritic cells, internalized antigens gain access to the cytosolic antigen-processing machinery and to the conventional MHC class I antigen-presentation pathway.

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Figure 1: MHC class I presentation of OVA-ICs by D1 dendritic cells, but not macrophages.
Figure 2: HRP internalized as ICs is delivered to the cytosol in D1 cells, but not in macrophages.
Figure 3: Cytosolic delivery of internalized antigen but not of lysosomal markers.
Figure 4: Cytosolic transport of internalized HRP and OVA.
Figure 5: Proteasomal degradation of internalized HRP.
Figure 6: Antigen delivery into the cytosol requires disaggregation of ICs.
Figure 7: Electron-microscopic analysis of IC transport to the cytosol.
Figure 8: Transport of internalized dextrans to the cytosol is size selective.

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Acknowledgements

We thank J.C. Antoine for providing macrophages, L. Cabanié for chromatography analysis, A. Trautman for advice on the T-cell Ca2+-activation experiments, M. Albert, P. Benaroch, and P. Pereira for helpful discussions and comments on the manuscript, W. Faigle for his help with Adobe Photoshop, J. M. Griffith for preparation of ultrathin cryosections, and R. Scriwaneck and D. Morineau for photographic work.

Correspondence and requests for materials should be addressed to S.A.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale U520, Institut Curie, Section de Recherche, Paris, 75005, France

    Ana Rodriguez, Armelle Regnault & Sebastian Amigorena

  2. Department of Cell Biology, UMC, Institute of Biomembranes, CX Utrecht, 3584, The Netherlands

    Monique Kleijmeer

  3. Department of Biotechnology and Bioscience, University of Milano-Bicocca, via L. Emmanuli 12 bis, Milan, 20126

    Paola Ricciardi-Castagnoli

  4. Italy,

    Paola Ricciardi-Castagnoli

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Rodriguez, A., Regnault, A., Kleijmeer, M. et al. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol 1, 362–368 (1999). https://doi.org/10.1038/14058

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