Hepatitis C virus mutation affects proteasomal epitope processing
J. Clin. Invest. Ulrike Seifert, et al. 114:250 doi:10.1172/JCI20985 [
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Figure 5Immunization of HLA-A2 transgenic mice with the wild-type HCV NS3 sequence induces more IFN-γ;–secreting and cytotoxic HCV NS3
1073–1081–specific CD8 T cells than immunization with the mutant HCV NS3 sequence. (
A and
B) Ex vivo analysis of NS31073–1081–specific, IFN-γ; producing CD8 T cells demonstrated a significantly greater response in mice immunized with wild-type than of mice immunized with mutant NS3 encoding vaccinia virus. In contrast, the response against the vaccinia virusH3L (VVH3L) epitope and the HCV NS3
1406–1414 epitope did not differ between both groups of mice. (
A) Dot plots from individual mice tested in the same experiment. (
B) Mean and standard deviation of the results of all 8 mice per group. (
C) Frequency of NS31073–1081-tetramer–specific T cells is higher in mice immunized with wild-type than in mice immunized with mutant HCV NS3 sequences. Mean and standard deviation of the results of 8 mice per group are shown. (
D) NS3
1073–1081-specific T cell lines from mice immunized with wild-type HCV NS3 sequences (WT) display greater cytotoxicity than those derived from mice immunized with mutant HCV NS3 (Mut). Mean and standard deviation of the results of 11 mice per group are shown.