Idiotype cascades associated with the CD4-HIV glycoprotein 120 interaction: Immunization with anti-idiotypic antibodies induces anti-anti-idiotypic responses with anti-CD4 specificity and in vitro neutralizing activity

Anti-idiotypic antibodies (Ab-2), which were generated in baboons against a mouse monoclonal antibody specific for the CD4 molecule expressed on human T cells, were used to produce anti-anti-idiotypic antibodies (Ab-3) in mic e, This response induced by Ab-2 immunization of BALB/c mice was classified as anti-anti-idiotype (Ab-3) on the basis of the ability of the mouse Ab-3 to (1) specifically bind the baboon Ab-2 preparation, but not irrelevant b aboon IgG preparations, (2) inhibit the binding of the anti-CD4 Ab-1 prepar ation to the baboon Ab-2, and (3) recognize a second baboon Ab-2, along wit h a rabbit Ab-2 specific for the monoclonal anti-CD4 Ab-1 preparation. The murine Ab-3 response also recognizes the CD4 molecule expressed on a human CD4(+) T cell line, as determined by flow cytometry; recognizes the same ep itopes on the CD4 molecule as the Ab-1; inhibits HIV-1 syncytium formation; and neutralizes HIV-1 primary isolates in vitro, These studies suggest tha t Ab-3 responses can be induced by anti-Id immunization, which serologicall y mimicks the antigen and Id specificities of the monoclonal anti-CD4 prepa ration used to generate the anti-Id. Thus, the Ab-3 response exhibits the c haracteristics of a population that represents the internal image of the Ab -1.