Exosome-driven antigen transfer for MHC class II presentation facilitated by the receptor binding activity of influenza hemagglutinin

J Immunol. 2010 Dec 1;185(11):6608-16. doi: 10.4049/jimmunol.1001768. Epub 2010 Nov 3.

Abstract

The mechanisms underlying MHC class I-restricted cross-presentation, the transfer of Ag from an infected cell to a professional APC, have been studied in great detail. Much less is known about the equivalent process for MHC class II-restricted presentation. After infection or transfection of class II-negative donor cells, we observed minimal transfer of a proteasome-dependent "class I-like" epitope within the influenza neuraminidase glycoprotein but potent transfer of a classical, H-2M-dependent epitope within the hemagglutinin (HA) glycoprotein. Additional experiments determined transfer to be exosome-mediated and substantially enhanced by the receptor binding activity of incorporated HA. Furthermore, a carrier effect was observed in that incorporated HA improved exosome-mediated transfer of a second membrane protein. This route of Ag presentation should be relevant to other enveloped viruses, may skew CD4(+) responses toward exosome-incorporated glycoproteins, and points toward novel vaccine strategies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Cell Line
  • Cell Line, Tumor*
  • Coculture Techniques
  • Exosomes / immunology*
  • Exosomes / metabolism*
  • Hemagglutinins, Viral / immunology
  • Hemagglutinins, Viral / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuraminidase / immunology
  • Neuraminidase / metabolism
  • Protein Binding / immunology
  • Protein Transport / immunology
  • Receptors, Virus / metabolism*

Substances

  • H-2M antigen, mouse
  • Hemagglutinins, Viral
  • Histocompatibility Antigens Class II
  • Receptors, Virus
  • hemagglutinin fusogenic peptide, influenza virus
  • Neuraminidase