tetano
Editor, Senior Moderator
Published ahead of print 26 September 2012, doi: 10.1128/JVI.01841-12
Cross-allele CTL responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals
Jun Liua,b,
Shihong Zhanga,b,c,
Shuguang Tana,b,c,
Yong Yid,
Bin Wue,
Bin Caof,
Fengcai Zhue,
Chen Wangf,
Hua Wange,
Jianxun Qia,b and
George F. Gaoa,b,c,g,#
aCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China
bChina-Japan joint laboratory of molecular immunology and molecular microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China
cCollege of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, 100049, China
dThe 306th Hospital of PLA, Beijing 100101, China
eJiangsu Provincial Center for Disease Control and Prevention (Jiangsu CDC), Nanjing 210009, China
fBeijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China
gResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China
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 to be presented by most, if not all, of the HLAs. Herein, 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) restricted manner. The cross-alelle antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the 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 elucidated 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.
http://jvi.asm.org/content/early/2012/09/20/JVI.01841-12.abstract
Cross-allele CTL responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals
Jun Liua,b,
Shihong Zhanga,b,c,
Shuguang Tana,b,c,
Yong Yid,
Bin Wue,
Bin Caof,
Fengcai Zhue,
Chen Wangf,
Hua Wange,
Jianxun Qia,b and
George F. Gaoa,b,c,g,#
aCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China
bChina-Japan joint laboratory of molecular immunology and molecular microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China
cCollege of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, 100049, China
dThe 306th Hospital of PLA, Beijing 100101, China
eJiangsu Provincial Center for Disease Control and Prevention (Jiangsu CDC), Nanjing 210009, China
fBeijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China
gResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China
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 to be presented by most, if not all, of the HLAs. Herein, 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) restricted manner. The cross-alelle antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the 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 elucidated 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.
http://jvi.asm.org/content/early/2012/09/20/JVI.01841-12.abstract