Linear and Conformational B Cell Epitope Prediction of the HER 2 ECD-Subdomain III by in silico Methods

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptorfamily of receptor tyrosine kinases that plays important roles in all processes of cell development. Theiroverexpression is related to many cancers, including examples in the breast, ovaries and stomach. Anticancertherapies targeting the HER2 receptor have shown promise, and monoclonal antibodies against subdomains IIand IV of the HER2 extra-cellular domain (ECD), Pertuzumab and Herceptin, are currently used in treatmentsfor some types of breast cancers. Since anti HER2 antibodies targeting distinct epitopes have different biologicaleffects 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 serverssuch as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then, Discotope, CBtope and SUPERFICIALsoftware tools were employed for conformational B cell epitope prediction. In contrast to previously reportedepitopes of HER2 ECD we predicted conformational B cell epitopes P1C: 378-393 (PESFDGDPASNTAPLQ) andP2C: 500-510 (PEDECVGEGLA) by the integrated strategy and P4: PESFDGD-X-TAPLQ; P5: PESFDGDP XTAPLQ; 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 antigensto actively immune mice for development of new monoclonal antibodies and peptide cancer vaccines that targetdifferent epitopes or structural domains of HER2 ECD.