ANTIGENIC STRUCTURE OF HEPATITIS C VIRUS

慢性丙型肝炎患者的增殖反应和CTL反应 重组DNA表达的多肽抗原和抗原的感染 在核心蛋白中定义了几个CTL表位， NS3、NS4和NS5。对这些表位的CTL反应正在研究中 患者了解CTL与慢性粒细胞白血病发病的关系 了解这些CTL反应是否与丙型肝炎有关 疾病的诱发或恢复。一种新的人类白细胞抗原A2限制性CTL 在NS3蛋白中发现了CTL表位。这篇墓志铭是 通过一种新技术发现的，这种技术既不需要合成肽，也不需要 基于已知A2基序的预测。这个表位确实不是一个已知的 A2主题。表达所有结构基因的裸露DNA疫苗和 NS3基因已被制备，并被证明在小鼠中具有抗原性。这个 高变区也被研究为T细胞表位的来源 在一个相对保守的区域发现了一个辅助表位。 所谓的高变区。这个辅助表位可能是 在调节该区域的免疫反应方面很重要。新的 正在研究体外中和的方法，包括 丙型肝炎病毒囊膜糖蛋白与细胞的结合试验，病毒减量 通过使用特定的T细胞系和 检测细胞内丙型肝炎病毒酶系统作为丙型肝炎病毒的一种检测方法 复制。这些检测中的几种也应该对抗病毒有用。 放映。 丙型肝炎是一个主要的公共卫生问题，目前正处于控制之下 预赛阶段。CBER积极参与新的 诊断性测试可用于改进血液筛查和 来源等离子体。CBER负责基于生物的 干扰素等治疗方法。试验性疫苗已经被 所描述的和第一个IND预计很快就会出现。治疗性疫苗 基于CTL的表位也正在被几个 实验室和公司。对肝炎免疫生物学的认识 C与我们已经授权的产品有直接关系 目前正在审查血液和血浆产品的筛查 以及已经获得许可并正在接受审查的治疗药物，例如 干扰素。再次了解丙型肝炎病毒感染的免疫学和 免疫病理机制对于我们对这些疾病的回顾将是至关重要的。 项目。

Both proliferative and CTL responses of patients with chronic HCV infections to peptide antigens and antigens expressed by recombinant DNA systems.Several CTL epitopes have been defined in the core protein, NS3,NS4 and NS5. CTL responses to these epitopes are being investigated in patients to understand the relationship of CTL to the pathogenesis of hepatitis C.It is important to know if these CTL responses are related to disease induction or to recovery from. A new HLA A2 restricted CTL epitope CTL epitpope was identified in the NS3 protein. This epitpoe was found by a novel technique that did not require synthesis of peptides nor prediction based on known A2 motifs. This epitope indeed was not a known A2 motif. Naked DNA vaccines expressing all the structural genes and the NS3 gene have been prepared and shown to be antigenic in mice. The hypervariable region has also been studied as a source of T cell epitopes ad a helper epitope has been identified in a relatively conserved region of the so called hypervariable region. This helper epitope may be important in regulating the immune response to that region. New approaches to in vitro neutralization are being studied including a binding assay for HCV envelope glycoproteins to cells, reduction in viral replication as measured by CTL assays usiing specific T cell lines and detection of intracellular HCV enzyme systems as a measure of HCV replication. Several of these assays should also be useful for antiviral screening. Hepatitis C is a major public health problem for which control is at a preliminary stage. CBER is actively involved in the licensing of new diagnostic tests that can be used to improve the screening of blood and source plasma. CBER ihas responsibility for biologic based therapeuticssuch as interferon. Experimental vaccines have already been described and the first IND's are expected shortly. Therapeutic vaccines based on CTL epitopes are also being actively pursued by several laboratories and companies. Understanding the immunobiology of hepatitis C has a direct relationship to the products that we have already licensed and are presently reviewing for screening blood and plasma products as well as therapeutics that have been licensed and are under review such as interferons. Again understanding the immunology of HCV infections and immunopathogenesis will be vitally important for our reviews of these projects.