Another discontinuous epitope on glycoprotein gp120 that is important in human immunodeficiency virus type 1 neutralization is identified by a monoclonal antibody.
To define the domains in the envelope glycoprotein important for antibody neutralization of the human immunodeficiency virus type 1 (HIV-1), monoclonal antibodies (mAbs) were generated by immunizing mice with purified glycoprotein gp120 of the IIIB isolate. One mAb, G3-4, reacted with the gp120 of homologous (IIIB) and heterologous (RF) isolates. In addition, mAb G3-4 efficiently neutralized both IIIB and RF viruses in vitro, as well as four of nine primary HIV-1 isolates. In competition immunoassays, mAb G3-4 and soluble CD4 were found to inhibit one another in binding to gp120. However, no competition was seen between mAb G3-4 and mAbs directed to the third variable region or the fourth conserved region of gp120. In particular, mAb G3-4 did not compete with our human mAb 15e, which identifies a discontinuous epitope on gp120 involved in group-specific neutralization of HIV-1 and in gp120-CD4 binding. Epitope-mapping studies on mAb G3-4 with synthetic or unglycosylated recombinant peptides were negative, suggesting that its epitope may be discontinuous. Indeed, this hypothesis was confirmed by showing the loss of mAb G3-4 serologic reactivity when gp120 was first denatured. We conclude that the site recognized by mAb G3-4 represents another discontinuous epitope on gp120 important for neutralization of HIV-1.
Ho
D D
DD
Aaron Diamond AIDS Research Center, New York University School of Medicine, NY 10016.
Fung
M S
MS
Cao
Y Z
YZ
Li
X L
XL
Sun
C
C
Chang
T W
TW
Sun
N C
NC
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens / Q000276:immunology*; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000032:analysis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains