Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus.
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.
Tu
Wenwei
W
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
Mao
Huawei
H
Zheng
Jian
J
Liu
Yinping
Y
Chiu
Susan S
SS
Qin
Gang
G
Chan
Ping-Lung
PL
Lam
Kwok-Tai
KT
Guan
Jing
J
Zhang
Lijuan
L
Guan
Yi
Y
Yuen
Kwok-Yung
KY
Peiris
J S Malik
JS
Lau
Yu-Lung
YL
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
D018984:Epitopes, T-Lymphocyte; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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