Chinese Science Bulletin

, Volume 48, Issue 18, pp 1962–1966 | Cite as

Screening of HLA-A2 restricted CTL epitopes using molecular simulation

  • Miao Geng
  • Yuzhang Wu
  • Zhihua Lin
  • Zhengcai Jia
  • Wei Zhou
  • Liyun Zou


A new technology has been established to screen CTL epitope by using molecular simulation and molecular dynamics. By using this technology, four peptides of MAGE-2 were screened and further identified by peptide binding assay and cytotoxic assay. Results showed that three candidate peptides had higher affinity to HLA-A2 molecule and were able to pulse CTL activitiesin vitro in human PBMC. The results indicated that identification of CTL epitopes with computer assistant could overcome the complicated experimental steps, particularly the peptide elution step, and could directly observe peptide-MHC-I compound binding pattern and could be used to screen CTL epitopes quickly.


CTL epitope HLA-A2 identification computer assistant molecular simulation 


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  1. 1.
    van Elsas, A., van der Burg, S. H., van der Minne, C. E. et al., Peptide-pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA-A* 0201-binding peptides from the Melan-A/MART-1 self antigen, Eur. J. Immunol., 1996, 26(8): 1683–1689.CrossRefGoogle Scholar
  2. 2.
    Bristol, J. A., Schlom, J., Abrams, S. I., Development of a murine mutant Ras CD8+ CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties, J. Immunol., 1998, 160(5): 2433–2441.Google Scholar
  3. 3.
    Manici, S., Sturniolo, T., Imro, M. A. et al., Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11, J. Exp. Med., 1999, 189(5): 871–876.CrossRefGoogle Scholar
  4. 4.
    Falk, K., Rotzschke, O., Stefanivic, S. et al., Allete-specific motifs revealed by squencing of self-peptides eluted from MHC molecules, Nature, 1991, 351: 290–296.CrossRefGoogle Scholar
  5. 5.
    Adams, H. P., Koziol, J. A., Prediction of binding to MHC class I molecules, J. Immunol. Methods, 1995, 185(2): 181–190.CrossRefGoogle Scholar
  6. 6.
    Sun, M., Che, Y., Miao, F. M. et al., Conformational analysis on anti-HIV-1 peptide T22([Tyr5,12,Lys7]-polyphemusinII), Chinese Science Bulletin, 2001, 46(20): 1685–1688.CrossRefGoogle Scholar
  7. 7.
    De Backer, O., Verheyden, A. M., Boon, T., Structure, chromosomal location, and expression pattern of three mouse genes homologous to the human MAGE genes, Genomics, 1995, 28(1): 74–83.CrossRefGoogle Scholar
  8. 8.
    Weynants, P., Lethe, B., Brasseur, F. et al., Expression of mage genes by non-small-cell lung carcinomas, Int. J. Cancer, 1994, 56(6): 826–829.CrossRefGoogle Scholar
  9. 9.
    Tahara, K., Mori, M., Sadanaga, N. et al., Expression of the MAGE gene family in human hepatocellular carcinoma, Cancer, 1999, 85(6): 1234–1240.CrossRefGoogle Scholar
  10. 10.
    Scarcella, D. L., Chow, C. W., Gonzales, M. F. et al., Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers, Clin-Cancer-Res., 1999, 5(2): 335–339.Google Scholar
  11. 11.
    Dalerba, P., Frascella, E., Macino, B. T. et al., MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas, Int-J-Cancer, 2001, 93(1): 85–90.CrossRefGoogle Scholar
  12. 12.
    Visseren, M. J., van der Burg, S. H., van der Voort, E. I. et al., Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specific MAGE-2 gene product, Int. J. Cancer, 1997, 73(1): 125–130.CrossRefGoogle Scholar
  13. 13.
    Geng, M., Jia, Z. C., Wan, Y. et al., Prediction of HLA-A2 restricted CTL epitope of tumor antigen MAGE-2, Acta Academiae Medicinae Militaris Tertiae (in Chinese), 2000, 22(10): 934–937.Google Scholar
  14. 14.
    Nijman, H. W., Houbiers, J. G., Vierboom, M. P. et al., Identification of peptide sequences that potentially trigger HLA-A2.1-restricted cytotoxic T lymphocytes [J], Eur. J. Immunol., 1993, 23(6): 1215–1219.CrossRefGoogle Scholar
  15. 15.
    Yoon, H., Chung, M. K., Min, S. S. et al., Synthetic peptides of human papillomavirus type 18 E6 harboring HLA-A2 motif can induce peptide-specific cytotoxic T-cell from peripheral blood mononuclear cell, Virus Research, 1998, 54: 23–29.CrossRefGoogle Scholar
  16. 16.
    Matsumura, M., Fremont, D. H., Peterson, P. A. et al., Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science, 1992, 257(5072): 927–935.CrossRefGoogle Scholar
  17. 17.
    Lim, J. S., Kim, S., Lee, H. G. et al., Selection of peptides that bind to the HLA-A2 molecule by molecular modeling. Molecular Immunlogy, 1996, 33(2): 221–230.CrossRefGoogle Scholar
  18. 18.
    McCammon, J. A., Harvey, S. C., Dynamics of protein and nucleic acid, London: Cambridge University Press, 1987, 150–270.Google Scholar

Copyright information

© Science in China Press 2003

Authors and Affiliations

  • Miao Geng
    • 1
  • Yuzhang Wu
    • 1
  • Zhihua Lin
    • 1
    • 2
  • Zhengcai Jia
    • 1
  • Wei Zhou
    • 1
  • Liyun Zou
    • 1
  1. 1.Institute of ImmunologyPLA Third Military Medical UniversityChongqingChina
  2. 2.College of BioengineeringChongqing Institute of TechnologyChongqingChina

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