Two major groups of neutralizing anti-gp120 antibodies exist in HIV-infected individuals. Evidence for epitope diversity around the CD4 attachment site.
The aim of this study was to dissect neutralizing anti-gp120 antibody populations in seropositive asymptomatic individuals. Murine anti-Id mAb were raised against polyclonal affinity-purified human anti-gp120 antibodies. These anti-Id mAb were used to fractionate anti-gp120 antibodies from a pool of HIV-positive sera into idiotypically distinct anti-gp120 antibody (Id+Ab) preparations. Immunochemical and neutralization studies indicated that all Id+Ab that neutralized HIV-1 in vitro interacted with either the V3 loop or the CD4 attachment site of gp120. The V3-specific Id+Ab neutralized HIV-1 in a strain-restricted manner. Id+Ab specific for the CD4 attachment site exhibited different spectra of neutralizing activities against multiple strains of HIV-1. This finding indicates that multiple, antigenically diverse epitopes reside around the CD4 attachment site of gp120. Significantly, depletion of the Id+Ab from affinity-purified total anti-gp120 antibodies abrogated most of the neutralizing activities of these antibodies, suggesting that neutralizing anti-gp120 antibodies consist of two major specificities, either to the V3 region or to the CD4 attachment site. The understanding of specificities and neutralizing activities of different anti-gp120 antibodies in seropositive healthy individuals will be helpful for designing effective vaccines and immunotherapeutic strategies for AIDS.
Chamat
S
S
IDEC Pharmaceuticals Corporation, La Jolla, CA 92037.
Nara
P
P
Berquist
L
L
Whalley
A
A
Morrow
W J
WJ
Köhler
H
H
Kang
C Y
CY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis*; D015483:HIV Antibodies / Q000032:analysis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007130:Immunoglobulin Idiotypes