期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 148, 期 2, 页码 296-306出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2249.2007.03340.x
关键词
cytotoxic T lymphocytes; epitopes; escape; human; influenza virus
类别
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)-gamma-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-gamma-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.
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