title: Human monoclonal antibody 2909 binds to pseudovirions expressing trimers but not monomeric HIV-1 envelope proteins.
abstract: A human anti-HIV monoclonal antibody (mAb), 2909, selected on the basis of its potent neutralizing activity against HIV-1SF162, recognizes a complex epitope V2/V3 present on intact virions but not on soluble gp120. To confirm the quaternary nature of the epitope, 2909 binding was tested against the pseudovirus SF162 wild type (WT) expressing trimers and/or an SF162 mutant expressing monomeric envelope proteins. The construction of the SF162 mutant was made by an alanine substitution of nine hydrophobic residues in the N-terminal heptad repeat region of gp41 molecules that failed to form trimers on the virus surface. Monoclonal Ab 2909 bound only to SF162 WT virions and transfected cells as determined by immunoprecipitation and flow cytometry, respectively, but showed no reactivity to the SF162 mutant expressing monomeric gp120. The data provide further evidence for the existence of a unique quaternary epitope V2/V3 on the surface of unliganded virus.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10010, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
mesh_terms: D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D020836:Protein Structure, Quaternary; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; C514793:gp120 protein, Human immunodeficiency virus 1