Open Access

Identification of human leukemia antigen A*0201‑restricted epitopes derived from epidermal growth factor pathway substrate number 8

  • Authors:
    • Baishan Tang
    • Weijun Zhou
    • Jingwen Du
    • Yanjie He
    • Yuhua Li
  • View Affiliations

  • Published online on: April 23, 2015     https://doi.org/10.3892/mmr.2015.3673
  • Pages: 1741-1752
  • Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

T‑cell‑mediated immunotherapy of hematological malignancies requires selection of targeted tumor‑associated antigens and T‑cell epitopes contained in these tumor proteins. Epidermal growth factor receptor pathway substrate 8 (EPS8), whose function is pivotal for tumor proliferation, progression and metastasis, has been found to be overexpressed in most human tumor types, while its expression in normal tissue is low. The aim of the present study was to identify human leukemia antigen (HLA)‑A*0201‑restricted epitopes of EPS8 by using a reverse immunology approach. To achieve this, computer algorithms were used to predict HLA‑A*0201 molecular binding, proteasome cleavage patterns as well as translocation of transporters associated with antigen processing. Candidate peptides were experimentally validated by T2 binding affinity assay and brefeldin‑A decay assay. The functional avidity of peptide‑specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood mononuclear cells of healthy volunteers were evaluated by using an enzyme‑linked immunosorbent spot assay and a cytotoxicity assay. Four peptides, designated as P455, P92, P276 and P360, had high affinity and stability of binding towards the HLA‑A*0201 molecule, and specific CTLs induced by them significantly responded to the corresponding peptides and secreted IFN‑γ. At the same time, the CTLs were able to specifically lyse EPS8‑expressing cell lines in an HLA‑A*0201‑restricted manner. The present study demonstrated that P455, P92, P276 and P360 were CTL epitopes of EPS8, and were able to be used for epitope‑defined adoptive T‑cell transfer and multi‑epitope‑based vaccine design.
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August-2015
Volume 12 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Tang B, Zhou W, Du J, He Y and Li Y: Identification of human leukemia antigen A*0201‑restricted epitopes derived from epidermal growth factor pathway substrate number 8. Mol Med Rep 12: 1741-1752, 2015
APA
Tang, B., Zhou, W., Du, J., He, Y., & Li, Y. (2015). Identification of human leukemia antigen A*0201‑restricted epitopes derived from epidermal growth factor pathway substrate number 8. Molecular Medicine Reports, 12, 1741-1752. https://doi.org/10.3892/mmr.2015.3673
MLA
Tang, B., Zhou, W., Du, J., He, Y., Li, Y."Identification of human leukemia antigen A*0201‑restricted epitopes derived from epidermal growth factor pathway substrate number 8". Molecular Medicine Reports 12.2 (2015): 1741-1752.
Chicago
Tang, B., Zhou, W., Du, J., He, Y., Li, Y."Identification of human leukemia antigen A*0201‑restricted epitopes derived from epidermal growth factor pathway substrate number 8". Molecular Medicine Reports 12, no. 2 (2015): 1741-1752. https://doi.org/10.3892/mmr.2015.3673