title: A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120.
abstract: Previous studies have demonstrated that the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the V3 loop of glycoprotein gp120. Antibodies prepared against this region using gp120 or peptides as immunogens have been predominantly HIV-1-isolate-specific. In the present studies, murine monoclonal antibodies (mAbs) were prepared against the HIV-1MN strain. One mAb, designated NM-01, was selected for its ability to neutralize both the MN and IIIB strains. Neutralization of H9-cell infectivity as determined by reverse transcriptase assay demonstrated an ID50 of less than 1 microgram/ml for both MN and IIIB. mAb NM-01 also blocked MN and IIIB infectivity in the MT-2 assay and inhibited their reactivity in syncytium formation. The results further demonstrate that mAb NM-01 binds to the V3 loop of gp120 at amino acids 312-326. This mAb reacted equally well with loop peptides from the MN, IIIB, RF, and CDC4 isolates. In contrast, there was less affinity with a similar peptide from the NY5 strain and little if any reactivity with loop peptides from the Z2, Z6, and ELI strains. We also demonstrate that peptides corresponding to the V3 loops of MN and IIIB, but not Z6, block neutralization of IIIB virus by mAb NM-01. These findings indicate that mAb NM-01 reacts with diverse HIV-1 isolates through the Gly-Pro-Gly-Arg sequence of the V3 loop.
authors.affiliation: Nissin Molecular Biology Institute, Inc., Boston, MA 02215.
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Terada
authors.forename: Y
authors.initials: Y
authors.lastname: Yoneda
authors.forename: K W
authors.initials: KW
authors.lastname: Shea
authors.forename: R F
authors.initials: RF
authors.lastname: Chambers
authors.forename: D M
authors.initials: DM
authors.lastname: Stroka
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: D W
authors.initials: DW
authors.lastname: Kufe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015151:Immunoblotting; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015699:HIV Envelope Protein gp120; D010455:Peptides