Synthesis and characterization of anti-idiotypic anti-T4 antibodies

We injected rabbits with purified monoclonal murine immunoglobulin (IgG1) or polyclonal antithyroxine antibodies (anti-T4) and polyclonal anti-triiodothyroacetic acid (anti-Triac) antibodies to stimulate the production of anti-idiotypic antibodies. Purified immunoglobulins from all five rabbits immunized with monoclonal primary antibodies were able to inhibit the interaction between [125I]T4 and the primary antibody. The preimmune sera were inactive. This effect was not due to endogenous T4 contamination or contamination with the injected primary antibody. Half-maximal inhibition of binding of primary antibody with anti-idiotype was between 1.6 and 30 micrograms of total immunoglobulins. Addition of normal mouse IgG1 did not alter the inhibitory effect of the anti-idiotypic antibody, suggesting that this effect is specific. These anti-idiotypic antibodies reacted differently with different polyclonal antibodies, reflecting the heterogeneous nature of polyclonal antibody populations. Polyclonal antibodies were less effective in stimulating anti-idiotypic antibody production. One polyclonal anti-T4 and one anti-Triac antibody produced weak anti-idiotypic antibody that had to be used at a concentration of > 600 micrograms of total immunoglobulins to be inhibitory. Both inhibited the binding of T4 to the monoclonal anti-T4 antibody. However, they were ineffective in inhibiting the function of their own antigen, the polyclonal anti-T4 or anti-Triac antibody. We tested the most potent anti-idiotypic antibodies for their ability to compete with T4 for other T4-binding proteins. Specific inhibition of T4 binding to thyroid-binding globulin was observed with half-maximal effect at approximately 450 micrograms of total IgG.(ABSTRACT TRUNCATED AT 250 WORDS)