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.
Mittelman
Abraham
A
Department of Medicine, Division of Oncology/Hematology, New York Medical College, Valhalla NY, USA.
Lucchese
Alberta
A
Sinha
Animesh A
AA
Kanduc
Darja
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D000917:Antibody Formation; D001943:Breast Neoplasms / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology*; D020543:Proteome / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009842:Oligopeptides; D020543:Proteome; D018719:Erb-b2 Receptor Tyrosine Kinases