title: Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus.
abstract: While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Using influenza A virus matrix protein 1 (M1(58-66)) epitope-specific CTLs isolated from healthy HLA-A2(+) individuals, we further found that M1(58-66) epitope-specific CTLs efficiently killed both M1(58-66) peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1(58-66)-specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1(58-66) epitope-specific CTLs in 20% (4/20) of HLA-A2(+) individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.
authors.affiliation: Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Room L7-58, 7/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong. wwtu@hkucc.hku.hk
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.forename: Huawei
authors.initials: H
authors.lastname: Mao
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Yinping
authors.initials: Y
authors.lastname: Liu
authors.forename: Susan S
authors.initials: SS
authors.lastname: Chiu
authors.forename: Gang
authors.initials: G
authors.lastname: Qin
authors.forename: Ping-Lung
authors.initials: PL
authors.lastname: Chan
authors.forename: Kwok-Tai
authors.initials: KT
authors.lastname: Lam
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000328:Adult; D056738:Cross Protection; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D004196:Disease Outbreaks; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology*; D007371:Interferon-gamma / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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