title: Production of human monoclonal antibodies specific for conformational and linear non-V3 epitopes of gp120.
abstract: Three IgG1 human monoclonal antibodies (MAbs) directed against conformational epitopes of the gp120 envelope protein of HIV-1 were produced, as was a single human MAb to a linear epitope spanning amino acids 487-509 in the C-terminal portion of gp120. All three conformation-dependent MAbs reacted optimally with recombinant gp120 (rgp120) captured on plastic via its carbohydrate moieties with Concanavalin A. These MAbs were able to block the interaction between recombinant CD4 (rCD4) and rgp120; they were also able to achieve 50% neutralization of HTLV-IIIB and MN strains of HIV-1 in a concentration range of 0.5-12.8 micrograms/mL. The MAb to the linear determinant is the first reported human MAb specific for the immunodominant portion of gp120; this MAb was most reactive with rgp120 when it was coated directly on plastic. It could neither inhibit rCD4-rgp120 binding nor neutralize either HTLV-IIIB or MN. The binding affinities of the four human MAbs for rgp120 in solution, reflected by their dissociation constants (Kd), ranged from 0.5 x 10(-8) to 7.5 x 10(-8) M.
authors.affiliation: Department of Pathology, New York University Medical Center, New York 10016.
authors.forename: S
authors.initials: S
authors.lastname: Karwowska
authors.forename: M K
authors.initials: MK
authors.lastname: Gorny
authors.forename: A
authors.initials: A
authors.lastname: Buchbinder
authors.forename: V
authors.initials: V
authors.lastname: Gianakakos
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Fuerst
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D015531:Radioimmunoprecipitation Assay
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