학술논문
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies
Document Type
Academic Journal
Author
Zhou, Tongqing; Zhu, Jiang; Wu, Xueling; Moquin, Stephanie; Zhang, Baoshan; Acharya, Priyamvada; Georgiev, Ivelin S.; Altae-Tran, Han R.; Chuang, Gwo-Yu; Joyce, Gordon M.; Do Kwon, Young; Longo, Nancy S.; Louder, Mark K.; Luongo, Timothy; McKee, Krisha; Schramm, Chaim A.; Skinner, Jeff; Yang, Yongping; Yang, Zhongjia; Zhang, Zhenhai; Zheng, Anqi; Bonsignori, Mattia; Haynes, Barton F.; Scheid, Johannes F.; Nussenzweig, Michel C.; Simek, Melissa; Burton, Dennis R.; Koff, Wayne C.; Mullikin, James C.; Connors, Mark; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D.
Source
Immunity. Aug 01, 2013 39(2):245-258
Subject
Language
English
ISSN
1074-7613
Abstract
SUMMARY: Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10 antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few—likely one—ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population. GRAPHICAL ABSTRACT: (Figure is included in full-text article.) HIGHLIGHTS