Conserved epitopes dominate cross‐CD8+ T‐cell responses against influenza A H1N1 virus among Asian populations |
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Authors: | Jun Liu Bin Wu Shihong Zhang Shuguang Tan Yeping Sun Zhujun Chen Yuanfang Qin Mingwei Sun Guoli Shi Ying Wu Meiyi Sun Na Liu Kaida Ning Ying Ma Bin Gao Jinghua Yan Fengcai Zhu Hua Wang George F. Gao |
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Affiliation: | 1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), , Beijing, China;2. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), , Beijing, China;3. Jiangsu Provincial Center for Disease Prevention and Control, , Nanjing, China;4. University of Chinese Academy of Sciences, , Beijing, China;5. College of Life Science, Anhui Agricultural University, , Hefei, China;6. School of Life Sciences, University of Science and Technology of China, , Hefei, China;7. Epigen Biotec, , Beijing, China;8. Yale University School of Medicine, , New Haven, CT, USA;9. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, , Beijing, China |
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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. |
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Keywords: | CD8+ T cell Conserved epitope Immunodominance Influenza A H1N1 virus TCR usage |
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