Exosome-driven antigen transfer for MHC class II presentation facilitated by the receptor binding activity of influenza hemagglutinin.
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.
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
James S
JS
Testa
Geraud S
GS
Apcher
Joseph D
JD
Comber
Laurence C
LC
Eisenlohr
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism*; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D011991:Receptors, Virus / Q000378:metabolism*
C489628:H-2M antigen, mouse; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D011991:Receptors, Virus; C458881:hemagglutinin fusogenic peptide, influenza virus; D009439:Neuraminidase