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

Manijeh Mahdavi, Hassan Mohabatkar, Mehrnaz Keyhanfar, Abbas Jafarian Dehkordi, Mohammad Rabbani
2012 Asian Pacific Journal of Cancer Prevention  
Asian Pacific J Cancer Prev, 13, 3053-3059 1988). While the cysteine-rich subdomains and are involved in the homodimerization and heterodimerization (Fiore, 1987; Pietras, 1995) . HER2 is highly expressed in a significant proportion of breast, ovarian, gastric, colon, prostate and lung cancers. HER2 overexpression in these cancers often correlates with Abstract Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases
more » ... or tyrosine kinases that plays 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 P1 C : 378-393 (PESFDGDPASNTAPLQ) and P2 C : 500-510 (PEDECVGEGLA) by the integrated strategy 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.
doi:10.7314/apjcp.2012.13.7.3053 fatcat:irib2d2ob5ddph26xqstfxnbgi