HLA CLASS-I-RESTRICTED HUMAN CYTOTOXIC T-CELLS RECOGNIZE ENDOGENOUSLY SYNTHESIZED HEPATITIS-B VIRUS NUCLEOCAPSID ANTIGEN
HLA CLASS-I-RESTRICTED HUMAN CYTOTOXIC T-CELLS RECOGNIZE ENDOGENOUSLY SYNTHESIZED HEPATITIS-B VIRUS NUCLEOCAPSID ANTIGEN
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DOI：
10.1073/pnas.88.23.10445
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
CHISARI, FV
中科院分区：
文献类型：
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作者：
BERTOLETTI, A;FERRARI, C;CHISARI, FV
由于缺乏可再生系统来选择性地扩增和表征病毒性肝炎患者外周血中HBV特异性细胞毒性T淋巴细胞（ctl），对负责清除乙型肝炎病毒（HBV）感染细胞的免疫效应机制的了解受到严重限制。通过使用HBV核衣壳合成多肽和自体或HLA i类匹配的HBV核衣壳转染物的顺序刺激策略，我们现在报告了急性乙型病毒性肝炎患者外周血中能够裂解表达内源性合成HBV核衣壳抗原的靶细胞的CTL的存在。CTL反应是受HLA- a2限制的，由cd8阳性T细胞介导，并且对单个表位具有特异性。位于HBV核心蛋白氨基酸残基11和27之间；这些残基与可分泌的前心源性乙型肝炎e抗原共享。表达这些蛋白的靶细胞的等效裂解表明它们的细胞内运输途径可能相交。目前的报告提供了明确的证据，证明人类急性HBV感染期间可诱导识别内源性合成HBV核衣壳抗原的HLA - i类限制性cd8阳性ctl，并建立了一种策略，可以详细分析HBV特异性ctl在病毒性肝炎免疫发病机制中所起的作用。
Knowledge of the immune effector mechanisms responsible for clearance of hepatitis B virus (HBV)-infected cells has been severely limited by the absence of reproducible systems to selectively expand and to characterize HBV-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of patients with viral hepatitis. By using a strategy involving sequential stimulation with HBV nucleocapsid synthetic peptides followed by autologous, or HLA class I-matched, HBV nucleocapsid transfectants, we now report the existence of CTLs able to lyse target cells that express endogenously synthesized HBV nucleocapsid antigen in the peripheral blood of patients with acute viral hepatitis B. The CTL response is HLA-A2 restricted, mediated by CD8-positive T cells, and specific for a single epitope, located between amino acid residues 11 and 27 of HBV core protein; these residues are shared with the secretable precore-derived hepatitis B e antigen. Equivalent lysis of target cells that express each of these proteins suggests that their intracellular trafficking pathways may intersect. The current report provides definitive evidence that HLA class I-restricted, CD8-positive CTLs that recognize endogenously synthesized HBV nucleocapsid antigen are induced during acute HBV infection in humans and establishes a strategy that should permit a detailed analysis of the role played by HBV-specific CTLs in the immunopathogenesis of viral hepatitis.