Development of an anti-idiotypic antibody reactive with an antibody defining the epitope RPAP in the MUC-1 epithelial mucin core.

C595 is a murine IgG3 monoclonal antibody (MAb) raised against human urinary mucin. C595 antibody binds to the protein core of the MUC-1 mucin (the polymorphic epithelial mucin, PEM) which is elevated in tissue and secretions from human breast carcinomas. The antibody defines the tetrameric epitope, RPAP. In the present study, a syngeneic anti-idiotypic MAb, 911, was raised in BALB/c mice against the C595 of C595 to its mucin core antigen. In turn, pre-blocking of C595 with a 20 amino-acid mucin core peptide specifically inhibited binding of 911 antibody to C595. Cross-reactivity of antibody 911 was only observed against the IgM MAb, 789/91, which has the same minimum antibody-binding epitope as C595, namely, RPAP. Syngeneic and xenogeneic anti-sera against 911 antibody displayed increased binding to heptameric peptide sequences containing the motif, RPA(P). The anti-idiotypic antibody 911 therefore appears to recognize a site within or close to the binding site of the C595 antibody and thus carries an internal image of the parental mucin epitope. Consequently, the 911 idiotypic network offers a promising model system to investigate the mechanism of anti-idiotype-induced tumour immunity.