Direct Proteasome-Independent Cross-Presentation of Viral Antigen by Plasmacytoid Dendritic Cells on Major Histocompatibility Complex Class I

Nat Immunol. 2008 May;9(5):551-7. doi: 10.1038/ni.1602. Epub 2008 Mar 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cross-Priming
  • Dendritic Cells / immunology*
  • Endosomes / metabolism
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Influenza A virus / immunology
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • Organelles / immunology
  • Proteasome Endopeptidase Complex
  • Receptors, Transferrin / metabolism

Substances

  • Antigens, Viral
  • Histocompatibility Antigens Class I
  • Receptors, Transferrin
  • Proteasome Endopeptidase Complex