Anti-idiotypic antibodies to human anti-gp120 antibodies bind recombinant and cellular human CD4.
The presence of anti-CD4 antibodies in sera of human immunodeficiency virus (HIV)-seropositive individuals has been recently documented, but its origin remains unknown. To test the hypothesis that anti-idiotypic antibodies to gp120, the HIV envelope glycoprotein with high affinity for CD4, mimic the configuration of gp120 and bind CD4, we performed two sets of experiments. First, we tested the possibility that anti-CD4 antibodies present in sera of a proportion of HIV-positive individuals exhibit variable region complementarity to autologous anti-gp120 antibodies. We show here that affinity-purified human anti-gp160 antibodies recognize specifically autologous affinity-purified anti-CD4 antibodies. We also demonstrate that antibodies to CD4 competitively inhibit anti-gp160 autologous antibodies binding to gp160. This implies that at least some anti-CD4 antibodies are directed towards idiotypic motifs located on anti-gp120 antibodies and that they may result from an anti-idiotypic response to anti-gp120 antibodies. In a second set of experiments, we examined the effect of anti-idiotypic immunization of experimental animals against human anti-gp120 antibodies. We found that anti-idiotypic antibodies produced in a rabbit immunized against affinity-purified human anti-gp120 antibodies specifically recognize recombinant and cellular human CD4, and that this interaction is competitively inhibited by soluble CD4. The data support the concept of idiotypic mimicry whereby anti-idiotypic antibodies produced against anti-gp120 antibodies recognize CD4, the cellular receptor of HIV.
Corre
J P
JP
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Février
M
M
Chamaret
S
S
Thèze
J
J
Zouali
M
M
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins