Identification of Relevant Conformational Epitopes on the HER2 Oncoprotein by Using Large Fragment Phage Display (LFPD)

Federico Gabrielli, Roberto Salvi, Chiara Garulli, Cristina Kalogris, Serena Arima, Luca Tardella, Paolo Monaci, Serenella M. Pupa, Elda Tagliabue, Maura Montani, Elena Quaglino, Lorenzo Stramucci, Claudia Curcio, Cristina Marchini, Augusto Amici

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere58358
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 28 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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