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Anti-CD4 antibodies directed to the N terminus of CD4 can inhibit human immunodeficiency virus (HIV) infection. Therefore, it has been proposed that some of these reagents may contain idiotypic determinants which conformationally model the binding site expressed on gp120. In this report, we have selected a panel of anti-CD4 monoclonal antibodies as idiotypic mimics of gp120 by employing cross-blocking techniques, and CD4 epitope mapping using site-directed mutagenesis. These studies suggest that only 4 out of the original panel of 12 would be expected to represent suitable candidates for modelling the gp120 binding site. Nevertheless, anti-idiotypic antisera raised against these antibodies failed to inhibit gp120 binding to CD4. This negative result may reflect the incomplete modelling of the virus binding site by anti-CD4, or the lack of internal image antibody in the anti-idiotypic preparations. Alternatively, the binding site on gp120 may not be accessible to antibody neutralization, excluding the possibility of an idiotypic vaccine to HIV based on anti-CD4 antibody as surrogate antigen.

Original publication

DOI

10.1002/eji.1830210624

Type

Journal article

Journal

Eur J Immunol

Publication Date

06/1991

Volume

21

Pages

1491 - 1498

Keywords

Animals, Antibodies, Anti-Idiotypic, Antibodies, Monoclonal, Antigens, CD4, Binding Sites, Epitopes, HIV, HIV Envelope Protein gp120, Immune Sera, Mice, Mice, Inbred BALB C, Rats