A new epitope peptide derived from hepatitis C virus 1b possessing the capacity to induce cytotoxic T-lymphocytes in HCV1b-infected patients with HLA-A11, -A31, and -A33

一种源自丙型肝炎病毒 1b 的新表位肽,能够在 HLA-A11、-A31 和 -A33 的 HCV1b 感染患者中诱导细胞毒性 T 淋巴细胞

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作者:Satoko Matsueda, Akira Yamada, Yukari Takao, Mayumi Tamura, Nobukazu Komatsu, Shigeru Yutani, Tatsuya Ide, Michio Sata, Kyogo Itoh

Background

Hepatitis C virus (HCV) frequently causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma after long-term persistent infection. Among various genotypes of HCV, HCV1b is resistant to standard interferon therapy, and thus the development of new treatment modality is needed.

Conclusion

Therefore, the peptide at positions 30-39 of the core protein could be an appropriate target molecule of specific immunotherapy for all HLA-A11(+), -A31(+), and -A33(+) patients with HCV1b-related diseases.

Results

To provide a scientific basis for specific immunotherapy for HCV1b, we investigated HCV1b-derived epitope peptides recognized by human leukocyte antigen (HLA)-A11, -A31, or -A33-restricted cytotoxic T-lymphocytes (CTLs), and report here three novel vaccine candidate peptides selected by both antibody screening and CTL-inducing capacity from among 46 peptides of conserved regions of HCV1b sequences with binding motifs to HLA-A11, -A31, and -A33. Significant levels of IgG reactive to each of the three peptides were detected in the plasma of more than 50% of the HCV1b(+) patients. One peptide at positions 30-39 of the core protein induced peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A11(+), -A31(+), and -A33(+) patients. The other two peptides at positions 35-43 of the core protein and at positions 918-926 of the non-structural protein 2 also induced peptide-specific CTLs from the PBMCs of HLA-A11(+) and -A33(+) patients.

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