Monoclonal and polyclonal humoral immune response to EC HER‐2/NEU peptides with low similarity to the host's proteome

We are studying peptide immunogenicity as a function of the similarity level to the host's proteome. By using as a model the breast/prostate cancer‐associated HER‐2/neu antigen, we analyzed the monoclonal and polyclonal humoral immune responses against HER‐2/neu peptide motifs not shared with the host proteome. We show here that (i) a mouse monoclonal antibody (MAb) raised against the extracellular domain (EC) of human HER‐2/neu oncoprotein recognized a linear peptide motif endowed with low similarity level to the mouse proteome; (ii) likewise, human sera from breast/prostate cancer patients preferentially recognized peptide fragments from the EC of the HER‐2/neu oncoprotein having sequences that are not present in the human proteome. Together with previous results obtained in other disease models (cervical cancer‐associated HPV16 E7 oncoprotein and Pemphigus vulgaris auto‐antigen desmoglein‐3), the present data suggest that a low level of sequence similarity to the host's proteome might be an important factor in shaping the pool of B cell epitopes. © 2002 Wiley‐Liss, Inc.

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