Identification of HLA-A*0201-restricted CD8+ T-cell epitope C64-72 from hepatitis B virus core protein
Identification of HLA-A*0201-restricted CD8+ T-cell epitope C64-72 from hepatitis B virus core protein
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DOI：
10.1016/j.intimp.2012.03.018
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发表时间：
2012-06-01
影响因子：
5.6
通讯作者：
Huang, Xinping
中科院分区：
文献类型：
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作者：
Liu, Qiuyan;Zheng, Yuanyuan;Huang, Xinping
针对慢性B型肝炎病毒（HBV）感染的潜在治疗性疫苗的功效取决于强的和多特异性T细胞应答的发展。CD 8（+）细胞毒性T淋巴细胞（CTL）对HBV核心抗原（HBcAg）的应答能力对HBV慢性感染的预后至关重要。在这项研究中，我们已经确定了以前未描述的HLA-A*0201限制性HBcAg特异性CTL表位（HBcAg（64-72），C64-72。ELMTLATWV）。12结合试验表明C64-72与HIA-A*0201分子具有较高的亲和力。在功能上，肽C64-72可以在体内（HLA-A2.1/K-b转基因小鼠）和体外（健康HLA-A2.1（+）供体的PBL）诱导肽特异性CTL，如分别用C64-72脉冲的12细胞或自体人树突状细胞（DC）刺激后的干扰素-γ（IFN-γ）分泌所证明的。HLA-A*0201-C64-72四聚体染色显示在C64 - 72刺激的CD 8（+）T细胞中存在大量C64-72特异性CTL。此外，用C64-72脉冲的自体DC刺激后，CTL的肽特异性细胞毒性反应性以及穿孔素和颗粒酶B的产生也增加。这些结果表明，新鉴定的表位C64-72有可能用于开发HBV感染的免疫治疗方法。(C)2012爱思唯尔有限公司版权所有。
The efficacy of a potential therapeutic vaccine against chronic hepatitis B virus (HBV) infection depends on the development of strong and multi-specific T cell responses. The potency of CD8(+) cytotoxic T lymphocyte (CTL) responses toward HBV core antigen (HBcAg) has been shown to be critical for the outcomes of HBV chronic infection. In this study we have identified a previously undescribed HLA-A*0201-restricted HBcAg-specific CTL epitope (HBcAg(64-72), C64-72. ELMTLATWV). 12 binding assay showed that C64-72 had high affinity to HIA-A*0201 molecule. Functionally, the peptide C64-72 could induce peptide-specific CTLs both in vivo (HLA-A2.1/K-b transgenic mice) and in vitro (PBLs of healthy HLA-A2.1(+) donors), as demonstrated by interferon-gamma (IFN-gamma) secretion upon stimulation with C64-72-pulsed 12 cells or autologous human dendritic cells (DCs) respectively. HLA-A*0201-C64-72 tetramer staining revealed the presence of a significant population of C64-72-specific CTLs in C64-72-stimulated CD8(+) T cells. Furthermore, the peptide-specific cytotoxic reactivity and the production of perforin and granzyme B of CTLs also increased after stimulation with C64-72-pulsed autologous DCs. These results indicate that the newly identified epitope C64-72 has potential to be used in the development of immunotherapeutic approaches to HBV infection. (C) 2012 Elsevier B.V. All rights reserved.