Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody
作者机构：State Key Laboratory of Cell BiologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of Sciences/University of Chinese Academy of SciencesShanghaiChina CAS Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiChinese Academy of Sciences/University of Chinese Academy of SciencesShanghaiChina School of Life Science and TechnologyShanghaiTech UniversityShanghaiChina CAS Key Laboratory of Synthetic Chemistry of Natural SubstancesShanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina College of BiologyHunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangshaChina National Laboratory of BiophysicsInstitute of BiophysicsChinese Academy of Sciences/University of Chinese Academy of Sciences BdjingBeijingChina Interdisciplinary Innovation Institute of Medicine&EngineeringBeijing Advanced Innovation Center for Big Data-Based Precision MedicineSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Nanjing Galaxy Biopharma Co.LtdNanjingChina Hepatology SectionFirst HospitalUniversity of JilinChangchunChina
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2021年第18卷第3期
页 面：675-685页
核心收录：
学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
基 金：supported by grants from the Chinese National 973 Program(2015CB554302) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)to B.S the Chinese National 973 Program(2015CB554300) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010205)to M the National Natural Science Foundation of China(31670172) Shanghai Science and Technology Innovation Action(16DZ1910100)to B.S Nanjing Galaxy Biopharma C.O
主 题：Hepatitis C virus neutralizing antibody inferred germline CDRH3 disulfide bridge motif
摘 要：Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine *** study of bNAbs arising in natural infection is essential in this *** generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C *** antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on *** describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad *** found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of *** motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding ***,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization ***,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce ***,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.
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