title: Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus.
abstract: It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
authors.affiliation: Benaroya Research Institute at Virginia Mason, University of Washington, Seattle, WA 98195, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Roti
authors.forename: Junbao
authors.initials: J
authors.lastname: Yang
authors.forename: DeAnna
authors.initials: D
authors.lastname: Berger
authors.forename: Laurie
authors.initials: L
authors.lastname: Huston
authors.forename: Eddie A
authors.initials: EA
authors.lastname: James
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006389:Hemagglutinins, Viral; D014764:Viral Proteins