DOI QR코드

DOI QR Code

Cross-immunizing potential of tumor MAGE-A epitopes recognized by HLA-A*02:01-restricted cytotoxic T lymphocytes

  • Huang, Ze-Min (Department of Immunology, Third Military Medical University) ;
  • Jia, Zheng-Cai (Biomedical Analysis Center, Third Military Medical University) ;
  • Tang, Jun (Department of Dermatology, the 105th Hospital of PLA) ;
  • Zhang, Yi (Department of Immunology, Third Military Medical University) ;
  • Tian, Yi (Department of Immunology, Third Military Medical University) ;
  • Ni, Dong-Jing (Department of Immunology, Third Military Medical University) ;
  • Wang, Fang (Biomedical Analysis Center, Third Military Medical University) ;
  • Wu, Yu-Zhang (Department of Immunology, Third Military Medical University) ;
  • Ni, Bing (Department of Immunology, Third Military Medical University)
  • Received : 2012.03.21
  • Accepted : 2012.05.03
  • Published : 2012.07.31

Abstract

Almost all melanoma cells express at least one member of the MAGE-A antigen family, making the cytotoxic T cells (CTLs) epitopes with cross-immunizing potential in this family attractive candidates for the broad spectrum of anti-melanoma immunotherapy. In this study, four highly homologous peptides (P264: FLWGPRALA, P264I9: FLWGPRALI, P264V9: FLWGPRALV, and P264H8: FLWGPRAHA) from the MAGE-A antigens were selected by homologous alignment. All four peptides showed high binding affinity and stability to HLA-A$^*02:01$ molecules, and could prime CTL immune responses in human PBMCs and in HLA-A$^*02:01/K^b$ transgenic mice. CTLs elicited by the four epitope peptides could cross-lyse tumor cells expressing the mutual target antigens, except MAGE-A11 which was not tested. However, CTLs induced by P264V9 and P264I9 showed the strongest target cell lysis capabilities, suggesting both peptides may represent the common CTL epitopes shared by the eight MAGE-A antigens, which could induce more potent and broad-spectrum antitumor responses in immunotherapy.

Keywords

References

  1. De Plaen, E., Arden, K., Traversari, C., Gaforio, J. J., Szikora, J. P., De Smet, C., Brasseur, F., van der Bruggen, P., Lethe, B., Lurquin, C., Brasseur, R., Chomez, P., De Backer, O., Cavenee, W. and Boon, T. (1994) Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 40, 360-369. https://doi.org/10.1007/BF01246677
  2. Jungbluth, A. A., Busam, K. J., Kolb, D., Iversen, K., Coplan, K., Chen, Y. T., Spagnoli, G. C. and Old, L. J. (2000) Expression of MAGE-antigens in normal tissues and cancer. Int. J. Cancer 85, 460-465. https://doi.org/10.1002/(SICI)1097-0215(20000215)85:4<460::AID-IJC3>3.0.CO;2-N
  3. Serrano, A., Lethe, B., Delroisse, J. M., Lurquin, C., De Plaen, E., Brasseur, F., Rimoldi, D. and Boon, T. (1999) Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries. Int. J. Cancer 83, 664-669. https://doi.org/10.1002/(SICI)1097-0215(19991126)83:5<664::AID-IJC16>3.0.CO;2-V
  4. Otte, M., Zafrakas, M., Riethdorf, L., Pichlmeier, U., Loning, T., Janicke, F. and Pantel, K. (2001) MAGE-A gene expression pattern in primary breast cancer. Cancer Res. 61, 6682-6687.
  5. Jia, Z. C., Tian, Y., Huang, Z. M., Wang, J. X., Fu, X. L., Ni, B. and Wu, Y. Z. (2011) Identification of a new MAGE-A10 antigenic peptide presented by HLA-A*0201 on tumor cells. Cancer Biol. Ther. 11, 395-400. https://doi.org/10.4161/cbt.11.4.14100
  6. Novellino, L., Castelli, C. and Parmiani, G. (2005) A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol. Immunother. 54, 187-207. https://doi.org/10.1007/s00262-004-0560-6
  7. Jia, Z. C., Ni, B., Huang, Z. M., Tian, Y., Tang, J., Wang, J. X., Fu, X. L. and Wu, Y. Z. (2010) Identification of two novel HLA-A*0201-restricted CTL epitopes derived from MAGE-A4. Clin. Dev. Immunol. 2010, 567594.
  8. van der Bruggen, P., Bastin, J., Gajewski, T., Coulie, P. G., Boel, P., De Smet, C., Traversari, C., Townsend, A. and Boon, T. (1994) A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur. J. Immunol. 24, 3038-3043. https://doi.org/10.1002/eji.1830241218
  9. Tourdot, S., Scardino, A., Saloustrou, E., Gross, D. A., Pascolo, S., Cordopatis, P., Lemonnier, F. A. and Kosmatopoulos, K. (2000) A general strategy to enhance immunogenicity of low-affinity HLA-A2. 1-associated peptides: implication in the identification of cryptic tumor epitopes. Eur. J. Immunol. 30, 3411-3421. https://doi.org/10.1002/1521-4141(2000012)30:12<3411::AID-IMMU3411>3.0.CO;2-R
  10. Parker, K. C., Bednarek, M. A., Hull, L. K., Utz, U., Cunningham, B., Zweerink, H. J., Biddison, W. E. and Coligan, J. E. (1992) Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2. J. Immunol. 149, 3580-3587.
  11. Valmori, D., Lienard, D., Waanders, G., Rimoldi, D., Cerottini, J. C. and Romero, P. (1997) Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. Cancer Res. 57, 735-741.
  12. Valmori, D., Gileadi, U., Servis, C., Dunbar, P. R., Cerottini, J. C., Romero, P., Cerundolo, V. and Levy, F. (1999) Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3. J. Exp. Med. 189, 895-906. https://doi.org/10.1084/jem.189.6.895
  13. Guillaume, B., Chapiro, J., Stroobant, V., Colau, D., Van Holle, B., Parvizi, G., Bousquet-Dubouch, M. P., Theate, I., Parmentier, N. and Van den Eynde, B. J. (2010) Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules. Proc. Natl. Acad. Sci. U.S.A. 107, 18599-18604. https://doi.org/10.1073/pnas.1009778107
  14. Nijman, H. W., Houbiers, J. G., Vierboom, M. P., van der Burg, S. H., Drijfhout, J. W., D'Amaro, J., Kenemans, P., Melief, C. J. and Kast, W. M. (1993) Identification of peptide sequences that potentially trigger HLA-A2.1-restricted cytotoxic T lymphocytes. Eur. J. Immunol. 23, 1215-1219. https://doi.org/10.1002/eji.1830230603
  15. Guttridge, M. G., Street, J., Thomas, M. and Darke, C. (1999) Identification of HLA-A*0224: implications for PCR-SSP HLA typing. Tissue Antigens 53, 190-193. https://doi.org/10.1034/j.1399-0039.1999.530210.x
  16. Tang, Y., Lin, Z., Ni, B., Wei, J., Han, J., Wang, H. and Wu, Y. (2007) An altered peptide ligand for naive cytotoxic T lymphocyte epitope of TRP-2(180-188) enhanced immunogenicity. Cancer Immunol. Immunother. 56, 319-329.
  17. Shinohara, M. L., Jansson, M., Hwang, E. S., Werneck, M. B., Glimcher, L. H. and Cantor, H. (2005) T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc. Natl. Acad. Sci. U.S.A. 102, 17101-17106. https://doi.org/10.1073/pnas.0508666102

Cited by

  1. Steroid hormone influence on melanomagenesis vol.417, 2015, https://doi.org/10.1016/j.mce.2015.09.020