Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

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 struct...

Full description

Saved in:
Bibliographic Details
Published inScience (American Association for the Advancement of Science) Vol. 333; no. 6049; pp. 1593 - 1602
Main Authors Wu, Xueling, Zhou, Tongqing, Zhu, Jiang, Zhang, Baoshan, Georgiev, Ivelin, Wang, Charlene, Chen, Xuejun, Longo, Nancy S., Louder, Mark, McKee, Krisha, O'Dell, Sijy, Perfetto, Stephen, Schmidt, Stephen D., Shi, Wei, Wu, Lan, Yang, Yongping, Yang, Zhi-Yong, Yang, Zhongjia, Zhang, Zhenhai, Bonsignori, Mattia, Crump, John A., Kapiga, Saidi H., Sam, Noel E., Haynes, Barton F., Simek, Melissa, Burton, Dennis R., Koff, Wayne C., Doria-Rose, Nicole A., Connors, Mark, Mullikin, James C., Nabel, Gary J., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R.
Format Journal Article
LanguageEnglish
Published Washington, DC American Association for the Advancement of Science 16.09.2011
The American Association for the Advancement of Science
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
OTHERNIH
These authors contributed equally to this work.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1207532