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emergence of infections by the novel avian influenza A(H7N9) virus has posed a threat to human health. Cross-immunity between A(H7N9) and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.<h4>Methods</h4>\u2003We investigated the cellular and humoral immune responses against A(H7N9) and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), by serological and T-cell-specific assays, in a healthy population. The molecular bases of the cellular and humoral antigenic variability of A(H7N9) were illuminated by structural determination.<h4>Results</h4>\u2003We not only found that antibodies against A(H7N9) were lacking in the studied population, but also revealed that both CD4<sup>+</sup> and CD8<sup>+</sup> T cells that cross-reacted with A(H7N9) were at significantly lower levels than those against the A(H1N1)pdm09 peptides with substitutions. Moreover, individual peptides for A(H7N9) with low cross-reactivity were identified. Structural determination indicated that substitutions within these peptides influence the antigenic variability of A(H7N9) through both major histocompatibility complex (MHC) binding and T-cell receptor docking.<h4>Conclusions</h4>\u2003The impact of antigenicity-dependent substitutions on cross-reactivity of T-cell immunity against the novel influenza virus A(H7N9) in the healthy population benefits the understanding of immune evasion of influenza viruses and provides a useful reference for universal vaccine development.","bibjson":{"author":[{"initials":"WJ","lastname":"Liu","name":"Liu WJ"},{"initials":"S","lastname":"Tan","name":"Tan S"},{"initials":"M","lastname":"Zhao","name":"Zhao M"},{"initials":"C","lastname":"Quan","name":"Quan C"},{"initials":"Y","lastname":"Bi","name":"Bi Y"},{"initials":"Y","lastname":"Wu","name":"Wu Y"},{"initials":"S","lastname":"Zhang","name":"Zhang S"},{"initials":"H","lastname":"Zhang","name":"Zhang H"},{"initials":"H","lastname":"Xiao","name":"Xiao H"},{"initials":"J","lastname":"Qi","name":"Qi J"},{"initials":"J","lastname":"Yan","name":"Yan J"},{"initials":"W","lastname":"Liu","name":"Liu W"},{"initials":"H","lastname":"Yu","name":"Yu H"},{"initials":"Y","lastname":"Shu","name":"Shu Y"},{"initials":"G","lastname":"Wu","name":"Wu G"},{"initials":"GF","lastname":"Gao","name":"Gao GF"}],"identifier":[{"id":"10.1093/infdis/jiw471","type":"doi"},{"id":"27738054","type":"pubmed"}],"issue":["12"],"journal":{"iso_abbreviation":"J Infect Dis","name":""},"pages":["1937-1946"],"title":"Cross-immunity Against Avian Influenza A(H7N9) Virus in the Healthy Population Is Affected by Antigenicity-Dependent Substitutions.","type":"article","url":"https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiw471","volume":["214"],"year":[2016]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"2.57","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4mj6"},"rcsb":{"url":"https://www.rcsb.org/structure/4mj6"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-A*11:01 binding \"TMVMELIRMIK\" at 2.57&#8491; resolution","unique_chain_count":3}}
