BACKGROUND:

?The emergence of infections by the novel avian influenza A (H7N9) virus has posed a threat to human health. Cross-immunity between H7N9 and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.

METHODS:

?We investigated the cellular and humoral immune responses against H7N9 and the 2009 pandemic H1N1 influenza viruses, by serological and T-cell-specific assays in a healthy population. The molecular bases of the cellular and humoral antigenic variability of H7N9 were illuminated by structural determination.

RESULTS:

?We not only found antibodies against H7N9 were lacking in the studied population, but also revealed both CD4+ and CD8+ T-cells that cross-reacted with H7N9 were at significantly lower levels than those against the 2009pH1N1 peptides with substitutions. Moreover, individual peptides for the H7N9 virus with low cross-reactivity were identified. Structural determination indicated that substitutions within these peptides influence the antigenic variability of H7N9 through both major histocompatibility complex (MHC)-binding and T-cell receptor (TCR)-docking.

CONCLUSIONS:

?The impact of antigenicity-dependent substitutions on cross-reactivity of T-cell immunity against the novel H7N9 virus in the healthy population benefits the understanding of immune evasion of influenza viruses and provides a useful reference for universal vaccine development.