Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus

[tetano]

J Virol. 2010 Apr 21. [Epub ahead of print]
Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus.

Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, Guan Y, Yuen KY, Peiris JM, Lau YL.

Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.
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 had not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce IFN-gamma and TNF-alpha. Using influenza A virus matrix protein 1 (M158-66) epitope-specific CTLs isolated from healthy HLA-A2(+) individuals, we further found that M158-66 epitope-specific CTLs efficiently killed both M158-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M158-66-specific CTLs showed 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 M158-66 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 provide some valuable implications for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

PMID: 20410263 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20410263?dopt=Abstract

 

[Giuseppe]

Re: Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus

[Source: US National Library of Medicine, (LINK). Edited.]

J Virol. 2010 Apr 21. [Epub ahead of print]

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus.

Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, Guan Y, Yuen KY, Peiris JM, Lau YL. - Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.

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 had not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce IFN-gamma and TNF-alpha. Using influenza A virus matrix protein 1 (M158-66) epitope-specific CTLs isolated from healthy HLA-A2(+) individuals, we further found that M158-66 epitope-specific CTLs efficiently killed both M158-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M158-66-specific CTLs showed 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 M158-66 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 provide some valuable implications for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

PMID: 20410263 [PubMed - as supplied by publisher]
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