Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Mahdavi, Manijeh (Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences) ;
  • Mohabatkar, Hassan (Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan) ;
  • Keyhanfar, Mehrnaz (Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan) ;
  • Dehkordi, Abbas Jafarian (Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences) ;
  • Rabbani, Mohammad (Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences)
  • Published : 2012.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor 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.

Keywords

References

  1. Ansari HR, Gajendra PS, Raghava GP (2010). Identification of conformational B-cell epitopes in an antigen from its primary sequence. Immunol Res, 6, 6. https://doi.org/10.1186/1745-7580-6-6
  2. Bonilla FA, Oettgen HC (2010). Adaptive immunity. J Allergy Clin Immunol, 125, 33-40. https://doi.org/10.1016/j.jaci.2009.09.017
  3. Boyer CM, Pusztai L, Wiener JR, et al. (1999). Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbb-2 (her-2/neu) gene product p185. Int J Cancer, 82, 525-31. https://doi.org/10.1002/(SICI)1097-0215(19990812)82:4<525::AID-IJC10>3.0.CO;2-J
  4. Bradford JR, Westhead DR (2005). Improved prediction of protein-protein binding sites using a support vector machines approach. Bioinform, 21, 1487-94. https://doi.org/10.1093/bioinformatics/bti242
  5. Calabrich A, Fernandes GS, Katz A (2008). Trastuzumab: mechanisms of resistance and therapeutic opportunities. Oncol (Williston Park), 22, 1250-8.
  6. Chen P, Rayner S, Hu KH (2011). Advances of Bioinformatics tools applied in virus epitopes prediction. Virologica sinica, 26, 1-7. https://doi.org/10.1007/s12250-011-3159-4
  7. Cho HS, Mason K, Ramyar KX, et al. (2003). Structure of the extracellular region of HER2 alone and in complex with the herceptin fab. Nature, 421, 756-60. https://doi.org/10.1038/nature01392
  8. Dakappagari NK, Lute KD, Rawale S, et al. (2005). Conformational HER-2/neu B-cell epitope peptide vaccine designed to incorporate two native disulfide bonds enhances tumor cell binding and antitumor activities. J Biol Chem, 280, 54-63. https://doi.org/10.1074/jbc.M411020200
  9. Dakappagari NK, Pyles J, Parihar R, et al. (2003). Chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. J Immunol, 170, 4242-53. https://doi.org/10.4049/jimmunol.170.8.4242
  10. Dakappagari N, Douglas D, Triozzi P, et al. (2000). Prevention of mammary tumors with a chimeric Her-2 B-cell epitope peptide vaccine. Cancer Res, 60, 3782-9.
  11. Disis ML, Cheever MA (1997). HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res, 71, 343-71. https://doi.org/10.1016/S0065-230X(08)60103-7
  12. Ercolini AM, Machiels JP, Chen YC, et al. (2003). Identification and character-ization of the immunodominant rat HER-2/neu MHC class I epitope presented by spontaneous mammary tumors from HER-2/neu-transgenic mice. J Immunol, 170, 4273-80. https://doi.org/10.4049/jimmunol.170.8.4273
  13. Fiore PD (1987). ErbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science, 237, 178-82. https://doi.org/10.1126/science.2885917
  14. Franklin MC, Carey KD, Vajdos FF, et al. (2004). Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell, 5, 317-28. https://doi.org/10.1016/S1535-6108(04)00083-2
  15. Garrett JT, Kaumaya P, Pei D, et al. (2007). Peptide based B cell epitope vaccines targeting HER-2/Neu. Degree of doctor of philosophy thesis in the graduate school of the Ohio State University.
  16. Goede A, Jaeger IS, Preissner R (2005). SUPERFICIAL-surface mapping of proteins via structure-based peptide library design. BMC Bioinform, 6, 223. https://doi.org/10.1186/1471-2105-6-223
  17. Haro I, Gomara MJ (2004). Design of synthetic peptidic constructs for the vaccine development against viral infections. Curr Protein Pept Sci, 5, 425-33. https://doi.org/10.2174/1389203043379314
  18. Haste Andersen P, Nielsen M, Lund O (2006). Prediction of residues in discontinuous B-cell epitopes using protein 3D structures. Protein Sci, 15, 2558-67. https://doi.org/10.1110/ps.062405906
  19. Ishida T, Tsujisaki M, Hinoda Y, et al. (1994). Establishment and characterization of mouse-human chimeric MAb to erbB-2 product. Jpn J Cancer Res, 85, 172-8. https://doi.org/10.1111/j.1349-7006.1994.tb02079.x
  20. Jasinska J, Wagner S, Radauer C, et al. (2003). Inhibition of tumor cell growth by antibodies induced after vaccination with peptides derived from the extracellular domain of HER-2/Neu. Int J Cancer, 107, 976-83. https://doi.org/10.1002/ijc.11485
  21. Jiang L, Zhou JM, Yin Y, et al. (2010). Selection and identification of B-cell epitope on NS1 protein of dengue virus type 2. Virus Res, 150, 49-55. https://doi.org/10.1016/j.virusres.2010.02.012
  22. Kulkarni-Kale U, Bhosle S, Kolaskar AS (2005). CEP: a conformational epitope prediction server. Nucleic Acids Res, 33, 168-71.
  23. Larsen JE, Lund O, Nielsen M (2006). Improved method for predicting linear B cell epitopes. Immunol Res, 2, 2. https://doi.org/10.1186/1745-7580-2-2
  24. Lax I (1988). Localization of a major receptor-binding domain for epidermal growth factor by affinity labeling. Mol Cell Bio, 8, 1831-4.
  25. Lebreton A, MoreauV, Lapalud P, et al. (2011). Discontinuous epitopes on the C2 domain of coagulation factor VIII mapped by computer-designed synthetic peptides. Brit J Hem, 155, 487-97. https://doi.org/10.1111/j.1365-2141.2011.08878.x
  26. Manzalawy Y, Dobbs D, Honavar V (2008b). Predicting flexible length linear B-cell epitopes. 7th international conference on computational systems bioinformatics. CA. 121-31.
  27. Manzalawy Y, Dobbs D, Honavar V (2008a). Predicting linear B-cell epitopes using string kernels. J Mol Rec, 21, 243-55. https://doi.org/10.1002/jmr.893
  28. Michalsky E, Goede A, Preissner R (2003). Loops In Proteins (LIP)-a comprehensive loop database for homology modelling. Protein Eng, 16, 979-85. https://doi.org/10.1093/protein/gzg119
  29. Mittelman A, Lucchese A, Sinha A, Kanduc D (2002). Monoclonal and polyclonal humoral immune response to EC HER-2/Neu peptides with low similarity to the host,s proteome. Int J Cancer, 98, 741-7. https://doi.org/10.1002/ijc.10259
  30. Miyako H, Kametani Y, Katano I, et al. (2011). Antitumor Effect of New HER2 peptide vaccination based on B cell epitope. Anticancer Res, 31, 3361-8.
  31. Montgomery R, Makary E, Schiffman K, et al. (2005). Endogenous anti-HER2 antibodies block HER2 phosphorylation and signaling through extracellular signal regulated kinase. Cancer Res, 65, 650-6.
  32. Moreau V, Fleury C, Piquer D, et al. (2008). PEPOP: computational design of immunogenic peptides. BMC Bioinform, 9, 71. https://doi.org/10.1186/1471-2105-9-71
  33. Park JW (2008). Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer, 8, 392-401. https://doi.org/10.3816/CBC.2008.n.047
  34. Pietras RJ (1995). HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene, 10, 2435-46.
  35. Ponomarenko J, Bui HH, Li W, et al. (2008). ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinform, 9, 514. https://doi.org/10.1186/1471-2105-9-514
  36. Richard A, Goldsby T, Kindt J, et al. (2000). Kubey Immonology. 5th ed. (W H Freeman and Co (Sd)).
  37. Rockberg J, Schwenk JM, Uhlen M (2009). Discovery of epitopes for targeting the human epidermal growth factor receptor 2 (HER2) with antibodies. Mol onco, 3, 238-47. https://doi.org/10.1016/j.molonc.2009.01.003
  38. Saha S, Raghava GP (2004) BcePred:Prediction of continuous B-cell epitopes in antigenic sequences using physicochemical properties. In: Nicosia G, Cutello V, Bentley PJ, Timis J, eds. ICARIS, Springer. Heidelberg. pp 197-204.
  39. Saha S, Raghava GP (2006). Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins, 65, 40-8. https://doi.org/10.1002/prot.21078
  40. Sakaguchi S (2000). Regulatory T cells: key controllers of immunologic selftolerance. Cell, 101, 455. https://doi.org/10.1016/S0092-8674(00)80856-9
  41. Siyi H, Zhiqiang Z, Liangwei L, et al. (2008). Epitope mapping and structural analyses of an anti-ErbB2 antibody A21: Molecular basis for tumor inhibitory mechanism. Proteins, 70, 938-49.
  42. Tai W, Mahato R, Cheng K (2010). The role of HER2 in cancer therapy and targeted drug delivery-Review. J Control Rel, 146, 264-75. https://doi.org/10.1016/j.jconrel.2010.04.009
  43. Veje Axelsena T, Holma A, Christiansena G, et al. (2011). Identification of the shortest AB-peptide generating highly specific antibodies against the C-terminal end of amyloid-B42. Vaccine, 29, 3260-9. https://doi.org/10.1016/j.vaccine.2011.02.026
  44. Vita R, Zarebski L, Greenbaum JA, et al. (2010). The immune epitope database 2.0. Nucleic Acids Res, 38, 854-62. https://doi.org/10.1093/nar/gkp1004
  45. Wang C, Li Y, Li P (2000). Generation and Characterization of monoclonal antibodies specific for the oncogene product P185 neu/c-erbB-2 by surface epitope masking (SEM). J Chin Immunol, 16, 539-41.
  46. Wang JN, Feng JN, Yua M, et al. (2004). Structural analyses of the epitopes on erbB2 interacted with inhibitory or non-inhibitor monoclonal antibodies. Mol Immunol, 40, 963-9. https://doi.org/10.1016/j.molimm.2003.09.012
  47. Wiwanitkit V (2007). Predicted B-cell epitopes of HER-2 oncoprotein by a bioinformatics method: a clue for breast cancer vaccine development. Asian Pac J Cancer Prev, 8, 137-8.
  48. Yum LY, Robyn LW (2002). Anti-ErbB2 monoclonal antibodies and ErbB2-directed vaccines. Cancer Immunol Immunother, 50, 569-87. https://doi.org/10.1007/s002620100226
  49. Zhang W, Xiong Y, Zhao M, et al. (2011). Prediction of conformational B-cell epitopes from 3D structures by random forests with a distance-based feature. BMC Bioinform, 12, 341. https://doi.org/10.1186/1471-2105-12-341

Cited by

  1. In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines vol.14, pp.10, 2013, https://doi.org/10.7314/APJCP.2013.14.10.5973
  2. Bioinformatic prediction of epitopes in the Emy162 antigen of Echinococcus multilocularis vol.6, pp.2, 2013, https://doi.org/10.3892/etm.2013.1142
  3. Immunization with a novel chimeric peptide representing B and T cell epitopes from HER2 extracellular domain (HER2 ECD) for breast cancer vol.35, pp.12, 2014, https://doi.org/10.1007/s13277-014-2503-y
  4. analysis vol.36, pp.7, 2014, https://doi.org/10.1111/pim.12111
  5. In silico docking of methyl isocyanate (MIC) and its hydrolytic product (1, 3-dimethylurea) shows significant interaction with DNA Methyltransferase 1 suggests cancer risk in Bhopal-Gas-Tragedy survivors vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7663
  6. Production and Characterization of New Anti-HER2 Monoclonal Antibodies vol.34, pp.3, 2015, https://doi.org/10.1089/mab.2014.0092
  7. In silico vaccine design against type 1 diabetes based on molecular modeling of coxsackievirus B4 epitopes vol.5, pp.1, 2016, https://doi.org/10.1007/s13721-016-0112-y
  8. Synthetic Peptides are Better Than Native Antigens for Development of ELISA Assay for Diagnosis of Tuberculosis vol.23, pp.2, 2017, https://doi.org/10.1007/s10989-016-9556-2
  9. In Silico Analysis of Synaptonemal Complex Protein 1 (SYCP1) and Acrosin Binding Protein (ACRBP) Antigens to Design Novel Multiepitope Peptide Cancer Vaccine Against Breast Cancer pp.1573-3904, 2018, https://doi.org/10.1007/s10989-018-9780-z