title: Identification of relevant conformational epitopes on the HER2 oncoprotein by using Large Fragment Phage Display (LFPD).
abstract: We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines.
authors.affiliation: Department of Bioscience and Biotechnology, University of Camerino, Camerino (MC), Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Gabrielli
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvi
authors.forename: Chiara
authors.initials: C
authors.lastname: Garulli
authors.forename: Cristina
authors.initials: C
authors.lastname: Kalogris
authors.forename: Serena
authors.initials: S
authors.lastname: Arima
authors.forename: Luca
authors.initials: L
authors.lastname: Tardella
authors.forename: Paolo
authors.initials: P
authors.lastname: Monaci
authors.forename: Serenella M
authors.initials: SM
authors.lastname: Pupa
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stramucci
authors.forename: Claudia
authors.initials: C
authors.lastname: Curcio
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D019151:Peptide Library; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C483804:Erbb2 protein, rat
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