HLA CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTES SPECIFIC FOR HEPATITIS-C VIRUS - IDENTIFICATION OF MULTIPLE EPITOPES AND CHARACTERIZATION OF PATTERNS OF CYTOKINE RELEASE
HLA CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTES SPECIFIC FOR HEPATITIS-C VIRUS - IDENTIFICATION OF MULTIPLE EPITOPES AND CHARACTERIZATION OF PATTERNS OF CYTOKINE RELEASE
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DOI：
10.1172/jci118287
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发表时间：
1995-11-01
影响因子：
15.9
通讯作者：
WALKER, BD
中科院分区：
文献类型：
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作者：
KOZIEL, MJ;DUDLEY, D;WALKER, BD
细胞毒性T淋巴细胞（CTL）对于控制病毒复制是重要的，并且它们的存在对于疾病结果可能是重要的。对丙型肝炎病毒（HCV）特异性CTL识别的蛋白质谱和这些细胞的功能特性的理解是理解疾病过程和持续感染机制的重要步骤，持续感染发生在大多数HCV感染个体中，在这份报告中，我们鉴定了受HLA I类分子A2、A3、A11、A23、B7、B8和B53限制的HCV特异性CTL应答。这些肝内CTL识别的表位符合已发表的与HLA I类分子结合的基序，尽管在某些情况下我们鉴定了不存在已发表基序的CTL表位，使用表达两种不同HCV毒株HCV-1和HCV-H的载体，揭示了毒株特异性和交叉反应性CTL。这些HCV特异性CTL显示以抗原和HLA I类特异性方式产生细胞因子，包括IFN-γ、TNF-α、GM-CSF、IL-8和IL-10，这些研究表明，CTL对HCV的反应是广泛定向的，并且在单个个体中可以靶向多达5个不同的表位。最小表位的鉴定可以促进肽特异性免疫策略。此外，这些细胞释放促炎细胞因子可能有助于HCV诱导的肝损伤的发病机制。
Cytotoxic T lymphocytes (CTL) are important to the control of viral replication and their presence may be important to disease outcome, An understanding of the spectrum of proteins recognized by hepatitis C virus (HCV)-specific CTL and the functional properties of these cells is an important step in understanding the disease process and the mechanisms of persistent infection, which occurs in the majority of HCV-infected individuals, In this report we identify HCV-specific CTL responses restricted by the HLA class I molecules A2, A3, A11, A23, B7, B8, and B53, The epitopes recognized by these intrahepatic CTL conform to published motifs for binding to HLA class I molecules, although in some cases we have identified CTL epitopes for which no published motif exists, The use of vectors expressing two different strains of HCV, HCV-1 and HCV-H, revealed both strain-specific and cross-reactive CTL, These HCV-specific CTL were shown to produce cytokines including IFN-gamma, TNF-alpha, GM-CSF, IL-8, and IL-10 in an antigen- and HLA class I-specific manner, These studies indicate that the CTL response to HCV is broadly directed and that as many as five different epitopes may be targeted in a single individual, The identification of minimal epitopes may facilitate peptide-specific immunization strategies, In addition, the release of proinflammatory cytokines by these cells may contribute to the pathogenesis of HCV-induced liver damage.