Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1.
A human immunoglobulin G1 lambda monoclonal antibody (MAb), 697-D, was developed that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1) gp120. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192 to 194 in the V2 loop of gp120 each completely abolished the binding capacity of 697-D in an enzyme-linked immunosorbent assay format. Competition analysis with three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697-D. The 697-D epitope is primarily conformation dependent, although there was weak reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment of recombinant gp120 HIVIIIB with sodium metaperiodate, which oxidizes carbohydrates, abolished the binding of the MAb, showing the dependence of the epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by its binding to the gp120 molecules from four of four laboratory isolates and five of five primary isolates. The MAb 697-D neutralized three out of four primary isolates but failed to neutralize any of four laboratory strains of HIV-1. 697-D and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing primary isolates, indicating that the V2 region of gp120, like the V3 region and the CD4-binding domain, can induce potent neutralizing antibodies against HIV-1 in humans.
Gorny
M K
MK
New York University Medical Center, New York.
Moore
J P
JP
Conley
A J
AJ
Karwowska
S
S
Sodroski
J
J
Williams
C
C
Burda
S
S
Boots
L J
LJ
Zolla-Pazner
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001483:Base Sequence; D001667:Binding, Competitive; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010504:Periodic Acid / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D012680:Sensitivity and Specificity; D017384:Sequence Deletion
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010504:Periodic Acid; C009288:metaperiodate