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新型HLA-A2限制的B,C型HBV特异性CTL表位的筛选及鉴定
  • 期刊名称:科学通报
  • 时间:0
  • 页码:2915-2924
  • 分类:Q811.4[生物学—生物工程]
  • 作者机构:[1]中国科学院微生物研究所,北京100101, [2]中国科学技术大学生命科学学院,合肥230026, [3]首都医科大学附属佑安医院,北京100069, [4]中国人民解放军第302医院,北京100039, [5]北京市地坛医院,北京100015
  • 相关基金:国家自然科学基金(30970146)和国家“十一五”传染病重大专项课题(2008ZX10002-005-3)资助项目
  • 相关项目:HLA-A24和-A33限制性B、C型乙肝病毒核心蛋白T细胞表位的鉴定与评价
中文摘要:

乙型肝炎病毒(HBV)特异性CD8+T细胞(CTL)介导的细胞免疫应答在控制HBV感染和病毒清除中至关重要,已鉴定的T细胞表位绝大多数都来自A,D基因型的乙肝病毒,而在我国流行的B,C型病毒表位研究较少.本研究合成重叠九肽肽库,通过细胞结合试验和体外重折叠实验系统筛选和鉴定B型和C型HBV核心蛋白表位,发现一个在60位氨基酸由L变异成V(L60V)而产生的新表位HBcAg60-68.表位肽能在HLA-A2/Kb转基因小鼠体内激发特异性CTL细胞免疫反应.检测HLA-A2阳性乙肝患者表位特异性CTL证明该九肽序列为体内自然加工的表位,这为研究HBV感染中特异性CTL免疫应答提供新的依据.

英文摘要:

Hepatitis B virus (HBV)-specific CD8+ T lymphocytes (CTL) play a major role in the control and clearance of HBV infection. However, the majority of human leukocyte antigen (HLA) class I restricted epitopes have been defined in HBV genotypes A and D, but definitions are lacking in genotypes B and C, which are prevalent in China. In this study, the overlapping 9-mer peptide pools were used to screen and identify genotypes B- and C-derived HBcAg-specific T cell epitopes by HLA stabilization assays and in vitro re-folding assays. We identified a new epitope derived from a leucine to valine mutation at position 60 of the core protein (L60V). This epitope can elicit CTL responses in HLA-A2/Kb transgenic mice. The defined HBV epitope was further characterized by investigating specific CTL responses in HLA-A2 positive patients with acute and chronic hepatitis B, indicating that the T cell epitope was naturally processed. These findings will provide a basis for the analysis of CTL responses in patients with HBV infection.

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