Recognition of influenza virus epitope variants by human CTL

Recently, an HLA-B£3501-restricted cytotoxic T-lymphocytes (CTL) epitope in the nucleoprotein (NP_418–426) of influenza A viruses was identified, which exhibited a high degree of variability. In the present study, the recognition of epitope variants by human cytotoxic T-lymphocytes (CTL) was investigated. Human CD8+ CTL clones were specific for NP_418–426 epitope variants within one subtype of influenza virus or cross-reactive with hetero-subtypic variants. Positions in the 9-mer were identified as determinants of CTL-specificity. The in vivo existence of T cells cross-reactive with homo- and hetero-subtypic variants of the epitope was confirmed with virus-specific polyclonal T cell populations obtained from HLA-B£3501+ blood donors. Based on CTL recognition patterns and the history of infection as assessed by serology, it was hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo.