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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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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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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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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DOI: https://doi.org/10.1038/ni.1602
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