The loss of immunodominant epitopes affects interferon-γ production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte response in vitro

Abstract

Summary In the present study, we examined the effect of the loss of the human leucocyte antigen (HLA)-B*3501-restricted nucleoprotein (NP)418–426 epitope on interferon (IFN)-γ-production and lytic activity of the human cytotoxic T lymphocyte (CTL) response in vitro. Extensive amino acid variation at T cell receptor contact residues of the NP418–426 epitope has led to repeated evasion from specific CTL. We generated recombinant influenza viruses with variants of the NP418–426 epitope, which were used to stimulate peripheral blood mononuclear cells obtained from six HLA-B*3501-positive study subjects in order to expand virus-specific CTL. Loss of the NP418–426 epitope resulted in a significant reduction of IFN-γ-expressing CD8+ T cells, similar to that observed previously after the loss of the HLA-B*2705-restricted NP383–391 epitope. In addition, the effect of the loss of the NP418–426 epitope on the lytic activity of the virus-specific CTL response was assessed. Also this functional property of the virus-specific CTL response was affected significantly by the loss of this and the NP383–391 epitope, as determined using the newly developed fluorescent antigen-transfected target cell (FATT)–CTL assay. These findings indicate that the loss of single immunodominant epitopes affects the functionality of the virus-specific CTL response significantly.