The loss of immunodominant epitopes affects interferon-γ production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte response in vitro
In the present study, we examined the effect of the loss of the human leucocyte antigen (HLA)-B*3501-restricted nucleoprotein (NP)418-426epitope 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 NP418-426epitope has led to repeated evasion from specific CTL. We generated recombinant influenza viruses with variants of the NP418-426epitope, 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 NP418-426epitope 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 NP383-391epitope. In addition, the effect of the loss of the NP418-426epitope 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 NP383-391epitope, 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.
|Keywords||Cytotoxic T lymphocytes, Epitopes, Escape, Human, Influenza virus|
|Persistent URL||dx.doi.org/10.1111/j.1365-2249.2007.03340.x, hdl.handle.net/1765/35453|
Berkhoff, E.G.M., Geelhoed-Mieras, M.M., Verschuren, E.J., van Baalen, C.A., Gruters, R.A., Fouchier, R.A.M., … Rimmelzwaan, G.F.. (2007). The loss of immunodominant epitopes affects interferon-γ production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte response in vitro. Clinical and Experimental Immunology, 148(2), 296–306. doi:10.1111/j.1365-2249.2007.03340.x