title: Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus.
abstract: In February 2013, zoonotic transmission of a novel influenza A virus of the H7N9 subtype was reported in China. Although at present no sustained human-to-human transmission has been reported, a pandemic outbreak of this H7N9 virus is feared. Since neutralizing antibodies to the hemagglutinin (HA) globular head domain of the virus are virtually absent in the human population, there is interest in identifying other correlates of protection, such as cross-reactive CD8(+) T cells (cytotoxic T lymphocytes [CTLs]) elicited during seasonal influenza A virus infections. These virus-specific CD8(+) T cells are known to recognize conserved internal proteins of influenza A viruses predominantly, but it is unknown to what extent they cross-react with the newly emerging H7N9 virus. Here, we assessed the cross-reactivity of seasonal H3N2 and H1N1 and pandemic H1N1 influenza A virus-specific polyclonal CD8(+) T cells, obtained from HLA-typed study subjects, with the novel H7N9 virus. The cross-reactivity of CD8(+) T cells to H7N9 variants of known influenza A virus epitopes and H7N9 virus-infected cells was determined by their gamma interferon (IFN-γ) response and lytic activity. It was concluded that, apart from recognition of individual H7N9 variant epitopes, CD8(+) T cells to seasonal influenza viruses display considerable cross-reactivity with the novel H7N9 virus. The presence of these cross-reactive CD8(+) T cells may afford some protection against infection with the new virus.
authors.affiliation: Viroscience Laboratory, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Carolien E
authors.initials: CE
authors.lastname: van de Sandt
authors.forename: Joost H C M
authors.initials: JH
authors.lastname: Kreijtz
authors.forename: Gerrie
authors.initials: G
authors.lastname: de Mutsert
authors.forename: Martina M
authors.initials: MM
authors.lastname: Geelhoed-Mieras
authors.forename: Marine L B
authors.initials: ML
authors.lastname: Hillaire
authors.forename: Stella E
authors.initials: SE
authors.lastname: Vogelzang-van Trierum
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002681:China / Q000453:epidemiology; D056738:Cross Protection; D003429:Cross Reactions; D004196:Disease Outbreaks; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012621:Seasons; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma