INDUCTION OF ANTIBODY-RESPONSES TO BREAST-CARCINOMA ASSOCIATED MUCINSUSING SYNTHETIC PEPTIDE CONSTRUCTS AS IMMUNOGENS

A strategy for directing and enhancing B cell immune responses against synthetic peptide determinants has been developed in order to produce antibodies specifically against protein epitopes of clinical relevanc e. A peptide sequence based upon the MUC-1 mucin protein core was sele cted for this purpose since anti-MUC-1 antibodies have proven diagnost ic application and therapeutic potential in human breast and ovarian c ancer. Peptide constructs were synthesised co-linearly linking the imm unodominant B cell determinant region, PDTRPAP, in the protein core of the MUC-1 mucin, to sequence 111-120 of influenza haemagglutinin A/X- 31, a determinant recognised by T helper cells through association wit h MHC class II molecules. Induction of anti-MUC-1 antibodies to the B cell determinant region by immunisation with peptide was shown to be d ependent upon both the presence and the position of the T cell determi nant. In addition, haplotype mismatching with respect to the T cell de terminant resulted in a significant lowering of the anti-MUC-1 antibod y response in peptide construct immunised mice. These findings are rel evant to the design of immunogens to produce antibodies against peptid e epitopes of tumour associated proteins and glycoproteins.