2011
Type(s)Journal Article
AuthorsWu, X. Zhou, T. Q. Zhu, Jiang Zhang, B. S. Georgiev, I. Wang, C. Chen, X. J. Longo, N. S. Louder, M. McKee, K. O'Dell, S. Perfetto, S. Schmidt, S. D. Shi, W. Wu, L. Yang, Y. P. Yang, Z. Y. Yang, Z. J. Zhang, Z. H. Bonsignori, M. Crump, J. A. Kapiga, S. H. Sam, N. E. Haynes, B. F. Simek, M. Burton, Dennis Koff, W. C. Doria-Rose, N. A. Connors, M. Mullikin, J. C. Nabel, G. J. Roederer, M. Shapiro, L. Kwong, P. D. Mascola, J. R. NISC Comparative Sequencing Program
SourceScience 2011 333:1593-1602
Urlhttp://dx.doi.org/10.1126/science.1207532
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.
Technology Platform
Next-Generation Sequencing
Research Topics
B cell Repertoire Analysis