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慢性乙型肝炎患者中针对乙型肝炎表面抗原的免疫优势 HLA-A*1101 限制性 CD8+ T 细胞反应。

An immunodominant HLA-A*1101-restricted CD8+ T-cell response targeting hepatitis B surface antigen in chronic hepatitis B patients.

机构信息

Department of Immunology, Third Military Medical University & Institute of Immunology, PLA, Chongqing 400038, PR China.

Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.

出版信息

J Gen Virol. 2013 Dec;94(Pt 12):2717-2723. doi: 10.1099/vir.0.052167-0. Epub 2013 Aug 30.

DOI:10.1099/vir.0.052167-0
PMID:23997182
Abstract

Hepatitis B virus (HBV) infection is a worldwide public health problem. HBV-specific CD8(+) CTLs are vital for viral clearance. Identification of immunodominant CTL epitopes from HBV-associated antigens is necessary for therapeutic vaccine development. We showed that the HLA-A1101 allele is one of the most common alleles in both healthy individuals and chronic hepatitis B (CHB) patients in the Chongqing area, China. However, less than 10% of epitopes of HBV-associated antigens have been identified in an HLA-A1101 context. Here, we describe an immunodominant CD8(+) T-cell response targeting a hepatitis B surface antigen determinant (HBs(295-304)) restricted by HLA-A1101 in both healthy individuals and CHB patients. Moreover, HBs(295-304) is more immunogenic for CTL induction than a known naturally HLA-A1101-processed epitope from hepatitis B core antigen (HBc(88-96)). Therefore, the newly identified epitope, HBs(295-304), will benefit the development of immunotherapeutic approaches for HBV infection.

摘要

乙型肝炎病毒(HBV)感染是一个全球性的公共卫生问题。HBV 特异性 CD8(+) CTL 对于病毒清除至关重要。鉴定与 HBV 相关抗原的免疫优势 CTL 表位对于治疗性疫苗的开发是必要的。我们表明,HLA-A1101 等位基因是中国重庆地区健康个体和慢性乙型肝炎(CHB)患者中最常见的等位基因之一。然而,在 HLA-A1101 背景下,只有不到 10%的 HBV 相关抗原的表位被鉴定出来。在这里,我们描述了针对乙型肝炎表面抗原决定簇(HBs(295-304))的免疫优势 CD8(+) T 细胞反应,该决定簇受 HLA-A1101 限制,在健康个体和 CHB 患者中均存在。此外,HBs(295-304)比乙型肝炎核心抗原(HBc(88-96))中已知的天然 HLA-A1101 处理表位更能诱导 CTL 反应。因此,新鉴定的表位 HBs(295-304)将有益于开发针对 HBV 感染的免疫治疗方法。

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