Antigenic and immunogenic mimicry of the HER2/neu oncoprotein by phage-displayed peptides

To recover peptides that antigenically and immunogenically mimic the p185^HER2 oncoprotein, we selected the phage-peptide libraries pVIII-9aa and pVIII-9aa. Cys using murine monoclonal antibodies (mAb) MGr2 and MGr6, directed against two distinct epitopes of the p185^HER2 extracellular domain. Phagedisplayed peptides containing consensus amino acid motifs were recovered and shown to compete specifically for mAb binding on tumor cells that overexpress p185^HER2. The deduced amino acid sequence of the peptides suggests that both epitopes defined by the mAb on p185^HER2 are discontinuous and that hydrophobic interactions are involved in binding with the mAb. A phage clone displaying the GPLDSLFAQ peptide elicited a specific immune response against the p185^HER2 in BALB/c mice, demonstrating that this phage-displayed peptide represents an immunological equivalent of the MGr2 epitope on p185^HER2 and might be used as a substitute for this oncoprotein in in vitro and in vivo immunological studies.