title: Cross-allele cytotoxic T lymphocyte responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals.
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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Shihong
authors.initials: S
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tan
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.forename: Fengcai
authors.initials: F
authors.lastname: Zhu
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D059871:HLA-A24 Antigen / Q000737:chemistry / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D059871:HLA-A24 Antigen; D015791:HLA-A3 Antigen