Differential processing of influenza nucleoprotein in human and mouse cells.
To investigate how early events in antigen processing affect the repertoire of peptides presented by MHC class I molecules, we compared the presentation of the influenza A nucleoprotein epitope 265-273 by HLA-A3 class I molecules in human and mouse cells. Mouse cells that express HLA-A3 failed to present the NP265-273 peptide when contained within the full-length nucleoprotein, to HLA-A3-restricted human cytotoxic T lymphocytes. However, when the epitope was generated directly in the cytosol using a recombinant vaccinia virus that expressed the nonamer peptide, mouse cells were recognized by HLA-A3-restricted CTL. Poor transport of the peptide by mouse TAP was not responsible for the defect as co-infection of mouse cells with recombinant vaccinia viruses encoding the full-length nucleoprotein and the human TAP1 and TAP2 peptide transporter complex failed to restore presentation. These results therefore demonstrate a differential processing of the influenza nucleoprotein in mouse and human cells. This polymorphism influences the repertoire of peptides presented by MHC class I molecules at the cell surface.
Braud
V M
VM
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB. vbraud@worf.molbiol.ox.ac.uk
McMichael
A J
AJ
Cerundolo
V
V
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000378:metabolism*; D001692:Biological Transport / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000378:metabolism; D015791:HLA-A3 Antigen / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007739:L Cells; D012515:Mast-Cell Sarcoma; D051379:Mice; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000276:immunology / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D000939:Epitopes; D015791:HLA-A3 Antigen; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; D014758:Viral Core Proteins; C071692:TAP2 protein, human