title: Contribution of hypervariable domains to the conformation of a broadly neutralizing glycoprotein 120 epitope.
abstract: Three of the five hypervariable domains (V1-V3) of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 have previously been shown to be dispensable for antigenic epitopes recognized by broadly neutralizing monoclonal antibodies. In this study, the influence of the V4 and V5 domains on an epitope recognized by a broadly neutralizing human monoclonal antibody, 1.5e, was investigated. In contrast with the V1, V2, and V3 domains of gp120, the V4 and V5 domains were found to be critical for binding to both CD4 and 1.5e. Our results suggest that V4 and V5 are in structurally less flexible regions of gp120 than V1, V2, and V3 and raises the question of whether variable domains V4 and V5 are also indispensable for other broadly neutralizing antibodies in the same class as 1.5e.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.forename: G
authors.initials: G
authors.lastname: Mazzara
authors.forename: Y L
authors.initials: YL
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Essex
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D001483:Base Sequence; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology; D000939:Epitopes / Q000737:chemistry*; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D017384:Sequence Deletion
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins