Wang Yi, Takao Yukari, Harada Mamoru, Komatsu Nobukazu, Ono Takeharu, Sata Michio, Itoh Kyogo, Yamada Akira
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Cell Immunol. 2006 May;241(1):38-46. doi: 10.1016/j.cellimm.2006.07.009. Epub 2006 Sep 11.
Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in preventing the spread of hepatitis C virus (HCV), vaccine-based HCV-specific CTL induction could be a promising strategy to treat HCV-infected patients. In this study, we tried to identify HCV2a-derived epitopes, which can induce human leukocyte antigen (HLA)-A24-restricted and peptide-specific CTLs. Peripheral blood mononuclear cells of HCV2a-infected patients or healthy donors were stimulated in vitro with HCV2a-derived peptides, which were prepared based on the HLA-A24 binding motif. As a result, three peptides (HCV2a 576-584, HCV2a 627-635, and HCV2a 1085-1094) efficiently induced peptide-specific CTLs from HLA-A24(+) HCV2a-infected patients as well as healthy donors. The cytotoxicity was exhibited by peptide-specific CD8(+) T cells in an HLA-A24-restricted manner. In addition, the HCV2a 627-635 peptide was frequently recognized by immunoglobulin G of HCV2a-infected patients. These results indicate that the identified three HCV2a peptides might be applicable to peptide-based immunotherapy for HLA-A24(+) HCV2a-infected patients.
由于病毒特异性细胞毒性T淋巴细胞(CTLs)在预防丙型肝炎病毒(HCV)传播中起关键作用,基于疫苗的HCV特异性CTL诱导可能是治疗HCV感染患者的一种有前景的策略。在本研究中,我们试图鉴定HCV2a衍生的表位,其可诱导人白细胞抗原(HLA)-A24限制性和肽特异性CTLs。用基于HLA-A24结合基序制备的HCV2a衍生肽在体外刺激HCV2a感染患者或健康供体的外周血单个核细胞。结果,三种肽(HCV2a 576-584、HCV2a 627-635和HCV2a 1085-1094)有效地从HLA-A24(+) HCV2a感染患者以及健康供体中诱导出肽特异性CTLs。细胞毒性由肽特异性CD8(+) T细胞以HLA-A24限制性方式表现出来。此外,HCV2a 627-635肽经常被HCV2a感染患者的免疫球蛋白G识别。这些结果表明,鉴定出的三种HCV2a肽可能适用于HLA-A24(+) HCV2a感染患者的基于肽的免疫治疗。