title: Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1.
abstract: We have isolated and characterized human monoclonal antibody 2G12 to the gp120 surface glycoprotein of human immunodeficiency virus type 1 (HIV-1). This antibody potently and broadly neutralizes primary and T-cell line-adapted clade B strains of HIV-1 in a peripheral blood mononuclear cell-based assay and inhibits syncytium formation in the AA-2 cell line. Furthermore, 2G12 possesses neutralizing activity against strains from clade A but not from clade E. Complement- and antibody-dependent cellular cytotoxicity-activating functions of 2G12 were also defined. The gp120 epitope recognized by 2G12 was found to be distinctive; binding of 2G12 to LAI recombinant gp120 was abolished by amino acid substitutions removing N-linked carbohydrates in the C2, C3, V4, and C4 regions of gp120. This gp120 mutant recognition pattern has not previously been observed, indicating that the 2G12 epitope is unusual. consistent with this, antibodies able to block 2G12 binding to recombinant gp120 were not detected in significant quantities in 16 HIV-positive human serum samples.
authors.affiliation: Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016, USA.
authors.forename: A
authors.initials: A
authors.lastname: Trkola
authors.forename: M
authors.initials: M
authors.lastname: Purtscher
authors.forename: T
authors.initials: T
authors.lastname: Muster
authors.forename: C
authors.initials: C
authors.lastname: Ballaun
authors.forename: A
authors.initials: A
authors.lastname: Buchacher
authors.forename: N
authors.initials: N
authors.lastname: Sullivan
authors.forename: K
authors.initials: K
authors.lastname: Srinivasan
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: H
authors.initials: H
authors.lastname: Katinger
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002460:Cell Line; D003176:Complement C3 / Q000276:immunology; D018604:Epitope Mapping; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011134:Polysaccharides / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D003176:Complement C3; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides