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Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I

Nature Immunology volume 9, pages 551–557 (2008)Cite this article

Abstract

Although plasmacytoid dendritic cells (pDCs) respond to virus replication in a nonspecific way by producing large amounts of type I interferon, a rapid, direct function for pDCs in activating antiviral lymphocytes is less apparent. Here we show that pDCs were able to rapidly initiate antigen-specific antiviral CD8+ T cell responses. After being exposed to virus, pDCs efficiently and rapidly internalized exogenous viral antigens and then presented those antigens on major histocompatibility complex (MHC) class I to CD8+ T cells. Processing of exogenous antigen occurred in endocytic organelles and did not require transit of antigen to the cytosol. Intracellular stores of MHC class I partially localized together with the transferrin receptor and internalized transferrin in endosomes, which suggested that such recycling endosomes are sites for loading peptide onto MHC class I or for peptide transit. Our data demonstrate that pDCs use 'ready-made' stores of MHC class I to rapidly present exogenous antigen to CD8+ T cells.

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Figure 1: Activated pDCs are powerful activators of allogeneic CD8+ T cells.
Figure 2: The pDCs cross-present influenza virus antigen more rapidly and efficiently than do mDCs.
Figure 3: MHC class I exists in large perinuclear intracellular pools in pDCs and rapidly translocates to the cell surface after viral activation of pDCs.
Figure 4: MHC class I is not located in the traditional endoplasmic reticulum-Golgi transport pathway in pDCs.
Figure 5: Intracellular stores of MHC class I are located in the recycling endosomal compartment in immature pDCs.

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Acknowledgements

We thank A.K. Palucka, M. Pypaert, J. Shay, Y. Xu and C. Xu. Anti-ERGIC-53 was provided by A. Satoh (Yale University School of Medicine). Supported by the Baylor Health Care Systems Foundation, the Dana Foundation (J.E.C.), the Ludwig Institute for Cancer Research, the National Institutes of Health (R01 CA078846-08, R01 AI068842-01 and U19 AI057234 to J.B.; R01 R37AI34098 to I.M.) and the Italian Foundation for Cancer Research (T.D.).

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Authors and Affiliations

  1. Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, 75204, Texas, USA

    Tiziana Di Pucchio, Sandra Clayton, Adam Palazzo, Monica Montes, Yaming Xue, Jacques Banchereau & John E Connolly

  2. Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 299, Rome, Italy

    Tiziana Di Pucchio

  3. Department of Cell Biology and Department of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, 06520, Connecticut, USA

    Bithi Chatterjee, Anna Smed-Sörensen & Ira Mellman

  4. Research Drug Discovery, Genentech, South San Francisco, 94080, California, USA

    Bithi Chatterjee, Anna Smed-Sörensen & Ira Mellman

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  1. Tiziana Di Pucchio
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Contributions

T.D. designed, did and analyzed experiments; B.C., A.S., J.E.C. and S.C. designed, did and analyzed imaging experiments; A.P. and Y.X. assisted in cellular isolation and analysis; M.M. provided influenza virus–specific T cell lines; J.E.C., J.B., I.M. and T.D. prepared the manuscript; J.B. and I.M. provided intellectual guidance on the project; and J.E.C. conceptualized and designed the project.

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Correspondence to Jacques Banchereau or John E Connolly.

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Tiziana Di Pucchio, Bithi Chatterjee, Anna Smed-Sörensen, Sandra Clayton, Adam Palazzo, Monica Montes, Yaming Xue, Ira Mellman, Jacques Banchereau & John E Connolly B.C., A.S.-S. and I.M. are employees of Genentech.

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Di Pucchio, T., Chatterjee, B., Smed-Sörensen, A. et al. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol 9, 551–557 (2008). https://doi.org/10.1038/ni.1602

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