Studies on the suppression of the immune response to a defined protein epitope by anti-idiotypic antibodies

We have previously reported that C3H.SW (CSW) and A/J mice immunized with the tobacco mosaic virus protein (TMVP) produce antibodies to a decapeptide epitope corresponding to amino acid residues 103-112 of the protein. In the C3H.SW (CSW) strain, the antibodies to the decapeptide contain major crossreactive idiotope, C10-IdX, which is found on a CSW-derived monoclonal antidecapeptide antibody, designated as C10. The in vivo administration of anti-C10 antibodies suppresses the response to the decapeptide epitope in CSW mice. The present communication describes experiments designed to elucidate several parameters responsible for the suppression produced by the in vivo administration of anti-C10. It was found that 50 micrograms of anti-C10 was required to suppress the response to the decapeptide in CSW mice when 2 weeks elapsed between administration of the anti-C10 and immunization with TMVP; however, only 10 ng was required when one injection of antigen instead of two was administered and when the interval between treatment with anti-C10 and immunization was extended to 6 weeks. This suggests that the anti-C10 induces alterations in the idiotypic network which are not yet fully developed after 2 weeks. Furthermore, experiments presented herein demonstrate that decapeptide-binding antibodies from A/J mice, which lack the C10-IdX, were also suppressed by pretreatment with anti-C10. Interestingly, unlike the case with the CSW strain, the titer to TMVP was decreased by the administration of anti-C10 to A/J mice which were subsequently immunized with TMVP. These findings suggest that the polyclonal anti-C10 contains antibodies to an idiotype which is a major component of the overall anti-TMVP response of A/J mice and may be important in the overall regulation of the anti-TMVP response.