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[利用噬菌体展示技术对丙型肝炎病毒蛋白抗原决定簇进行表位作图]

[Epitope mapping of antigenic determinants of hepatitis C virus proteins by phage display].

作者信息

Rechkina E A, Denisova G F, Masalova O V, Lideman L F, Denisov D A, Lesnova E I, Ataullakhanov R I, Gur'ianova S V, Kushch A A

出版信息

Mol Biol (Mosk). 2006 Mar-Apr;40(2):357-68.

Abstract

Study of individual hepatitis C (HCV) proteins could help to find a molecular structure and conformation, localization of antigenic and immunogenic determinants, to reveal of protective epitopes. It is necessary for practical medicine - development of diagnostic test-systems, vaccines and therapeutics. Linear and conformation dependent epitopes of HCV proteins was localized in this work and immunogenic properties of phage displayed peptides screened on monoclonal antibodies to HCV proteins have been investigated. Eleven epitopes of four HCV proteins have been studied. Three epitopes was found as linear, two epitopes were dependent on secondary structure of proteins and one epitope was dependent on tertiary structure of NS3 protein. Aminoacid sequences of other determinants have been determined and the distinct localization of these determinants will be continued after discovering of tertiary structure of HCV proteins. It was shown, that phage mimotope 3f4 is immunogenic and could induce specific hu- moral immune response to NS5A HCV protein. The data obtained could be useful for improving of HCV diagnostic test-systems, studying of amino acid substitutions and its influence on antigenic properties of the HCV proteins. The results could help to study an immune response in patients infected with different genotypes of HCV. Phage displayed peptides mimicking the antigenic epitopes of HCV proteins could be applied to development of HCV vaccine.

摘要

对丙型肝炎病毒(HCV)单个蛋白的研究有助于找到其分子结构和构象、抗原及免疫原性决定簇的定位,从而揭示保护性表位。这对于实际医学——诊断测试系统、疫苗和治疗药物的开发而言是必要的。在这项研究中确定了HCV蛋白的线性和构象依赖性表位,并研究了在针对HCV蛋白的单克隆抗体上筛选出的噬菌体展示肽的免疫原性。对四种HCV蛋白的11个表位进行了研究。发现3个表位为线性表位,2个表位依赖于蛋白质的二级结构,1个表位依赖于NS3蛋白的三级结构。已确定了其他决定簇的氨基酸序列,在发现HCV蛋白的三级结构后将继续研究这些决定簇的不同定位。结果表明,噬菌体模拟表位3f4具有免疫原性,可诱导针对HCV NS5A蛋白的特异性体液免疫反应。所获得的数据可用于改进HCV诊断测试系统、研究氨基酸取代及其对HCV蛋白抗原特性的影响。这些结果有助于研究感染不同基因型HCV患者的免疫反应。模拟HCV蛋白抗原表位的噬菌体展示肽可应用于HCV疫苗的开发。

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