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 mice. 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 baboon IgG preparations, (2) inhibit the binding of the anti-CD4 Ab-1 preparation to the baboon Ab-2, and (3) recognize a second baboon Ab-2, along with 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 epitopes on the CD4 molecule as the Ab-1; inhibits HIV-1 syncytium formation; and neutralizes HIV-1 primary isolates in vitro. These studies suggest that Ab-3 responses can be induced by anti-Id immunization, which serologically mimicks the antigen and Id specificities of the monoclonal anti-CD4 preparation used to generate the anti-Id. Thus, the Ab-3 response exhibits the characteristics of a population that represents the internal image of the Ab-1.
Shearer
M H
MH
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Dalgleish
A G
AG
Chanh
T C
TC
Kennedy
R C
RC
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D015726:Giant Cells; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010215:Papio; D011817:Rabbits
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018985:Epitopes, B-Lymphocyte; D007130:Immunoglobulin Idiotypes