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Updated: May 18, 2026
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Linear and conformational B cell epitope prediction of the HER 2 ECD-subdomain III by in silico methods
Manijeh Mahdavi1, Hassan Mohabatkar, Mehrnaz Keyhanfar
1Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases that play important roles in all processes of cell development. Their overexpression is related to many cancers, including examples in the breast, ovaries and stomach. Anticancer therapies targeting the HER2 receptor have shown promise, and monoclonal antibodies against subdomains II and IV of the HER2 extra-cellular domain (ECD), Pertuzumab and Herceptin, are currently used in treatments for some types of breast cancers. Since anti HER2 antibodies targeting distinct epitopes have different biological effects on cancer cells; in this research linear and conformational B cell epitopes of HER2 ECD, subdomain III, were identified by bioinformatics analyses using a combination of linear B cell epitope prediction web servers such as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then, Discotope, CBtope and SUPERFICIAL software tools were employed for conformational B cell epitope prediction. In contrast to previously reported epitopes of HER2 ECD we predicted conformational B cell epitopes P1C: 378-393 (PESFDGDPASNTAPLQ) and P2C: 500-510 (PEDECVGEGLA) by the integrated strategy and and P4: PESFDGD-X-TAPLQ; P5: PESFDGDP X TAPLQ; P6: ESFDGDP X NTAPLQP; P7: PESFDGDP-X-NTAPLQ; P8: ESFDG-XX-TAPLQPEQL and P9: ESFDGDP- X-NTAPLQP by SUPERFICIAL software. These epitopes could be further used as peptide antigens to actively immune mice for development of new monoclonal antibodies and peptide cancer vaccines that target different epitopes or structural domains of HER2 ECD.
Insights
Researchers identified new B cell epitopes on the Human Epidermal Growth Factor Receptor 2 (HER2) extracellular domain. These findings could lead to novel peptide cancer vaccines and monoclonal antibodies targeting HER2-overexpressing cancers.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Human Epidermal Growth Factor Receptor 2 (HER2) overexpression is linked to various cancers, including breast, ovarian, and stomach cancers.
- Current HER2-targeted therapies, like monoclonal antibodies Pertuzumab and Herceptin, target specific extracellular domain (ECD) subdomains.
- Distinct epitopes on HER2 ECD elicit different biological responses, necessitating further epitope characterization.
Purpose of the Study:
- To identify linear and conformational B cell epitopes within subdomain III of the HER2 ECD using bioinformatics.
- To predict novel epitopes that can serve as targets for developing advanced cancer immunotherapies.
Main Methods:
- Utilized a combination of bioinformatics web servers (ABCpred, BCPREDs, Bepired, Bcepred, Elliprro) for linear B cell epitope prediction.
- Employed Discotope, CBtope, and SUPERFICIAL software for conformational B cell epitope prediction.
- Integrated multiple prediction tools to enhance epitope identification accuracy.
Main Results:
- Identified novel conformational B cell epitopes P1C (378-393) and P2C (500-510) within HER2 ECD subdomain III.
- Predicted additional potential epitopes (P4-P9) using SUPERFICIAL software, characterized by specific amino acid sequences and potential gaps.
- These predicted epitopes differ from previously reported HER2 ECD epitopes.
Conclusions:
- The identified linear and conformational epitopes represent potential targets for new cancer therapies.
- These epitopes can be used as peptide antigens for active immunization in mice to develop novel monoclonal antibodies.
- The findings support the development of peptide cancer vaccines targeting specific HER2 ECD epitopes or structural domains.
