ANTIIDIOTYPIC 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 gp 120, the HIV envelope glycoprotein with high affinity for CD4, mimic the configuration of gp 120 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 complementary to autologous anti-gp 120 antibodies. We show here that affinity-purified human anti-gp 160 antibodies recognize specifically autologous affinity-purified anti-CD4 anti-bodies. We also demonstrate that antibodies to CD4 competitively inhibit anti-gp 160 autologous antibodies binding to gp 160. This implies that at least some anti-CD4 antibodies are directed towards idiotypic motifs located on anti-gp 120 antibodies and that they may result from an anti-idiotypic response to anti-gp 120 antibodies. In a second set of experiments, we examined the effect of anti-idiotypic immunization of experimental animals against human anti-gp 120 antibodies. We found that anti-idiotypic antibodies produced in a rabbit immunized against affinity-purified human anti-gp 120 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-gp 120 antibodies recognize CD4, the cellular receptor of HIV.