Human CD4 "internal antigen" mimicry by anti-idiotypic monoclonal antibodies.
Of 1019 hybridomas generated from a BALB/c mouse immunized with the syngeneic anti-CD4 monoclonal antibody HP2/6, 3 were found to secrete anti-idiotypic antibodies. Detailed analysis of anti-idiotypic monoclonal antibodies F16-10F6, F16-14D6 and F16-16D7 showed they recognize idiotope(s) not expressed by any of the anti-CD4 monoclonal antibodies tested, including those which inhibit the binding of HP2/6 to CD4 antigen. The idiotope recognized by the three anti-idiotypic antibodies are within (or closely related to) the antigen combining site of the immunizing antibody and distinct and spatially distant from the idiotope defined by monoclonal antibody F11-2302 which was previously shown to be outside the antigen combining site of HP2/6. Although F16-14D6 and F16-16D7 are indistinguishable in isotype, binding titer to idiotopes, fine specificity on a panel of monoclonal antibodies, relation to the combining site and competitive binding, it is likely that they are structurally different and recognize two distinct combining site-related idiotopes on HP2/6, as they display different spectrotypes and induce anti-anti-idiotypic (Ab3) immune sera with different specificities. Analysis of the fine specificity of the two Ab3 immune sera suggest they share idiotopes with HP2/6 and contain antibodies reacting with CD4 antigen. Among the latter, those induced with F16-14D6 display a different CD4 epitope specificity than HP2/6. Hence, anti-idiotypic antibodies F16-14D6 and F16-16D7 behave as "network antigen" for human CD4; idiotope-triggered antibody cascade may have a role in changing the specificities of antibody.
Perosa
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Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Medical School, Italy.
Dammacco
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F
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region