Epitopes described in "Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing."

Article Authors:Xueling Wu; 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; NISC Comparative Sequencing Program; James C Mullikin; Gary J Nabel; Mario Roederer; Lawrence Shapiro; Peter D Kwong; John R Mascola
Article Title:Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.
Reference Detail
Reference ID:1026961
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.
Affiliations:Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Reference Type:Literature
PubMed ID:21835983
Journal Volume:333
Article Pages:1593-602
Journal ISSN:1095-9203
Article Chemical List:AIDS Vaccines;Antibodies, Neutralizing;Antigens, CD4;Complementarity Determining Regions;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;Immunoglobulin Fab Fragments;Immunoglobulin Heavy Chains;Immunoglobulin J-Chains;Immunoglobulin Light Chains
Article MeSH List:AIDS Vaccines; Amino Acid Sequence; Antibodies, Neutralizing(chemistry; genetics; immunology; isolation & purification); Antibody Affinity; Antibody Specificity; Antigens, CD4(metabolism); Base Sequence; Binding Sites; Binding Sites, Antibody; Complementarity Determining Regions(genetics); Crystallography, X-Ray; Epitopes; Evolution, Molecular; Genes, Immunoglobulin Heavy Chain; HIV Antibodies(chemistry; genetics; immunology; isolation & purification); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV Infections(immunology); HIV-1(chemistry; immunology); High-Throughput Nucleotide Sequencing; Humans; Immunoglobulin Fab Fragments(chemistry; immunology); Immunoglobulin Heavy Chains(chemistry; immunology); Immunoglobulin J-Chains(genetics); Immunoglobulin Light Chains(chemistry; immunology); Models, Molecular; Molecular Sequence Data; Mutation; Sequence Analysis, DNA
Curation Last Updated:2015-06-05 04:18:49