Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals
Identifieur interne : 000815 ( Ncbi/Curation ); précédent : 000814; suivant : 000816Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals
Auteurs : Jun Liu [République populaire de Chine] ; Shihong Zhang [République populaire de Chine] ; Shuguang Tan [République populaire de Chine] ; Yong Yi [République populaire de Chine] ; Bin Wu [République populaire de Chine] ; Bin Cao [République populaire de Chine] ; Fengcai Zhu [République populaire de Chine] ; Chen Wang [République populaire de Chine] ; Hua Wang [République populaire de Chine] ; Jianxun Qi [République populaire de Chine] ; George F. Gao [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2012.
Abstract
Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24+ population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11+ and HLA-A24+ donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11+ population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.
Url:
DOI: 10.1128/JVI.01841-12
PubMed: 23015716
PubMed Central: 3503122
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<author><name sortKey="Yi, Yong" sort="Yi, Yong" uniqKey="Yi Y" first="Yong" last="Yi">Yong Yi</name>
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<author><name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name>
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<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
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<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
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<affiliation wicri:level="3"><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
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<wicri:regionArea>College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:aff id="aff7">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff>
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<wicri:regionArea>Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing</wicri:regionArea>
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<series><title level="j">Journal of Virology</title>
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<front><div type="abstract" xml:lang="en"><p>Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24<sup>+</sup>
population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11<sup>+</sup>
and HLA-A24<sup>+</sup>
donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11<sup>+</sup>
population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.</p>
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