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在人类白细胞抗原 - A24阳性且感染丙型肝炎病毒2a型(HCV2a)的患者中鉴定具有诱导细胞毒性T淋巴细胞能力的丙型肝炎病毒2a型衍生表位肽。

Identification of hepatitis C virus (HCV) 2a-derived epitope peptides having the capacity to induce cytotoxic T lymphocytes in human leukocyte antigen-A24+ and HCV2a-infected patients.

作者信息

Wang Yi, Takao Yukari, Harada Mamoru, Komatsu Nobukazu, Ono Takeharu, Sata Michio, Itoh Kyogo, Yamada Akira

机构信息

Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

出版信息

Cell Immunol. 2006 May;241(1):38-46. doi: 10.1016/j.cellimm.2006.07.009. Epub 2006 Sep 11.

Abstract

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.

摘要

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。

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