| Literature DB >> 21835983 |
Xueling Wu1, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A Crump, Saidi H Kapiga, Noel E Sam, Barton F Haynes, Melissa Simek, Dennis R Burton, Wayne C Koff, Nicole A Doria-Rose, Mark Connors, James C Mullikin, Gary J Nabel, Mario Roederer, Lawrence Shapiro, Peter D Kwong, John R Mascola.
Abstract
Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.Entities:
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Year: 2011 PMID： 21835983 PMCID： PMC3516815 DOI： 10.1126/science.1207532
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728