Human Cytotoxic T Lymphocytes Directed to Seasonal Influenza A Viruses Cross-React with the Newly Emerging H7N9 Virus

Influenza B virus-specific CD8+ T-lymphocytes strongly cross-react with viruses of the opposing influenza B lineage

“…The amino acid sequence identity of all viral proteins was very high between both lineages, which already suggested the existence of cross-reactive Tcell epitopes, as was also demonstrated for influenza A viruses (van de Sandt et al, 2014a). For the in silico prediction of epitopes, we excluded proteins encoded by the HA and NA gene segments, as these proteins undergo antigenic drift after positive selection by antibodies.…”

“…The percentage amino acid sequence identity of influenza A viral proteins has proven to be a good predictor of cross-reactivity of virus-specific T-cells with influenza A virus of various subtypes (van de Sandt et al, 2014a). Therefore, we wished to compare the overall amino acid sequence identity between the influenza B viruses used in the present study.…”

“…The main function of CTLs is to detect and eliminate virus-infected cells, thereby restricting viral replication and accelerating viral clearance (Sridhar et al, 2013;van de Sandt et al, 2012 Lee et al, 2008;Quinones-Parra et al, 2014;van de Sandt et al, 2014a;Yewdell et al, 1985) and their contribution to cross-protective immunity has been demonstrated in various animal models (Flynn et al, 1998;Hillaire et al, 2011;Kreijtz et al, 2007Kreijtz et al, , 2009O'Neill et al, 2000;Weinfurter et al, 2011). Although in vivo evidence for the role of CTLs in protective heterosubtypic immunity in humans is limited (Epstein, 2006;McMichael et al, 1983;Slepushkin, 1959;Sridhar et al, 2013), several in vitro studies have demonstrated that human CTLs directed to seasonal influenza A viruses cross-react with possible pandemic influenza A viruses, including avian influenza viruses of the H5N1 and H7N9 subtype and swine origin vH3N2 viruses (Hillaire et al, 2013;Jameson et al, 1999;Kreijtz et al, 2008;Lee et al, 2008;Quinones-Parra et al, 2014;van de Sandt et al, 2014a). Virus-specific CTLs are also induced after influenza B virus infections (Robbins et al, 1989(Robbins et al, , 1995(Robbins et al, , 1997 …”

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“…The cross-protective immune response is possible if the epitopes of the conservative influenza virus proteins that are known to be predominantly recognized by the T-lymphocytes (CD4 + and CD8 + ) are presented effectively [28]. As was shown in animal models, the cell immune response might have a protective role in case of homological and heterological infections [29][30][31][32][33][34][35]. The results of the adaptive transfer of T-cells from the primed mice to the naive recipients prove the protective function of the CD4 + and CD8 + cells [36].…”

Reassortant viruses for influenza vaccines: is it time to reconsider their genome structures?

“…However, in the past few decades, intensive studies of influenza-related immune responses have revealed that internal and nonstructural proteins of the influenza virus have an important impact on cellmediated immune (CMI) responses. Numerous studies have demonstrated the establishment of functional influenza virusspecific CD8 + and CD4 + T cells after both intranasal and intramuscular immunization with either IIV or LAIV [3][4][5].…”