title: HLA class I molecules consistently present internal influenza epitopes.
abstract: Cytotoxic T lymphocytes (CTL) limit influenza virus replication and prevent morbidity and mortality upon recognition of HLA class I presented epitopes on the surface of virus infected cells, yet the number and origin of the viral epitopes that decorate the infected cell are unknown. To understand the presentation of influenza virus ligands by human MHC class I molecules, HLA-B*0702-presented viral peptides were directly identified following influenza infection. After transfection with soluble class I molecules, peptide ligands unique to infected cells were eluted from isolated MHC molecules and identified by comparative mass spectrometry (MS). Then CTL were gathered following infection with influenza and viral peptides were tested for immune recognition. We found that the class I molecule B*0702 presents 3-6 viral ligands following infection with different strains of influenza. Peptide ligands derived from the internal viral nucleoprotein (NP(418-426) and NP(473-481)) and from the internal viral polymerase subunit PB1 (PB1(329-337)) were presented by B*0702 following infection with each of 3 different influenza strains; ligands NP(418-426), NP(473-481), and PB1(329-337) derived from internal viral proteins were consistently revealed by class I HLA. In contrast, ligands derived from hemagglutinin (HA) and matrix protein (M1) were presented intermittently on a strain-by-strain basis. When tested for immune recognition, HLA-B*0702 transgenic mice responded to NP(418-426) and PB1(329-337) consistently and NP(473-481) intermittently while ligands from HA and M1 were not recognized. These data demonstrate an emerging pattern whereby class I HLA reveal a handful of internal viral ligands and whereby CTL recognize consistently presented influenza ligands.
authors.affiliation: Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Wahl
authors.forename: Fredda
authors.initials: F
authors.lastname: Schafer
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bardet
authors.forename: Rico
authors.initials: R
authors.lastname: Buchli
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Air
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D015793:HLA-B7 Antigen; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009698:Nucleoproteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006680:HLA Antigens; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1