DEVELOPMENT OF AN ANTIIDIOTYPIC ANTIBODY-REACTIVE WITH AN ANTIBODY DEFINING THE EPITOPE R P A P 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, R P A P. In the present study, a syngeneic anti-idiotypic MAb, 911, was raised in BALB/c mice against the C595 antibody. This IgG2a anti-idiotypic antibody blocked the binding 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 91 1 antibody to C595. Cross-reactivity of antibody 91 1 was only observed against the IgM MAb, 789/9 1, which has the same minimum antibody-binding epitope as C595, namely, R P A P. Syngeneic and xenogeneic anti-sera against 91 1 antibody displayed increased binding to heptameric peptide sequences containing the motif, R P A(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 91 1 idiotypic network offers a promising model system to investigate the mechanism of anti-idiotype-induced tumour immunity. (C) 1993 Wiley-Liss, Inc.