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-Structure paper
タイトル | Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor. |
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ジャーナル・号・ページ | Immunity, Vol. 44, Issue 4, Page 939-950, Year 2016 |
掲載日 | 2016年4月19日 |
著者 | Leopold Kong / Bin Ju / Yajing Chen / Linling He / Li Ren / Jiandong Liu / Kunxue Hong / Bin Su / Zheng Wang / Gabriel Ozorowski / Xiaolin Ji / Yuanzi Hua / Yanli Chen / Marc C Deller / Yanling Hao / Yi Feng / Fernando Garces / Richard Wilson / Kaifan Dai / Sijy O'Dell / Krisha McKee / John R Mascola / Andrew B Ward / Richard T Wyatt / Yuxing Li / Ian A Wilson / Jiang Zhu / Yiming Shao / |
PubMed 要旨 | VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain ...VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability. |
リンク | Immunity / PubMed:27067056 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.9 - 22.0 Å |
構造データ | EMDB-6372: EMDB-6373: PDB-5cd3: PDB-5cd5: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM / VRC01 / HIV-1 / CD4 binding site / gp120 / antibody |