title: Conserved epitopes dominate cross-CD8+ T-cell responses against influenza A H1N1 virus among Asian populations.
abstract: Novel strains of influenza A viruses (IAVs) have emerged with high infectivity and/or pathogenicity in recent years, causing worldwide concern. T cells are correlated with protection in humans through cross-reactive immunity against heterosubtypes of IAV. However, the different hierarchical roles of IAV-derived epitopes with distinct levels of polymorphism in the cross-reactive T-cell responses against IAV remain elusive. In this study, immunodominant epitopes scattered throughout the entire proteome of 2009 pandemic influenza A H1N1 virus and seasonal IAVs were synthesized and divided into different pools depending on their conservation. The overall profile of the IAV-specific CD8(+) T-cell immunity was detected by utilizing these peptide pools and also individual peptides. A dominant role of the conserved peptide-specific T-cell immunity was illuminated within the anti-IAV responses, while the CD8(+) T-cell responses against the variable epitopes were lower than the conserved peptides. As previously demonstrated within a Caucasian population, we determined that GL9-specific T cells, which also utilize Vβ 17 TCR (BV19), play a pivotal role in IAV-specific T-cell immunity within an HLA-A2(+) Asian population. Our study objectively reveals the different predominant roles of T-cell epitopes among IAV-specific cross-reactive cellular immunity. This may guide the development of vaccines with cross-T-cell immunogenicity against heterosubtypes of IAV.
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: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Shihong
authors.initials: S
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tan
authors.forename: Yeping
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Chen
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Qin
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sun
authors.forename: Guoli
authors.initials: G
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Meiyi
authors.initials: M
authors.lastname: Sun
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Kaida
authors.initials: K
authors.lastname: Ning
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: Fengcai
authors.initials: F
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000328:Adult; D000940:Antigenic Variation; D001208:Asia; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020543:Proteome; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D020543:Proteome; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins
keywords: CD8+ T cell; Conserved epitope; Immunodominance; Influenza A H1N1 virus; TCR usage