Abstract
The humanMAGE3 gene is expressed in a significant proportion of tumors of various histological types, but is silent in normal adult tissues other than testis and placenta. Antigens encoded byMAGE3 may therefore be useful targets for specific antitumor immunization. Two antigenic peptides encoded by theMAGE3 gene have been reported previously. One is presented to cytolytic T lymphocytes (CTL) by HLA-A1, the other by HLA-A2 molecules. Here we show that MAGE3 also codes for a peptide that is presented to CTL by HLA-1344.MAGE3 peptides containing the HLA-1344 peptide binding motif were synthesized. Peptide MEVDPIGHLY, which showed the strongest binding to HLA-1344, was used to stimulate blood T lymphocytes from normal HLA-1344 donors. CTL clones were obtained that recognized not only HLA-B44 cells sensitized with the peptide, but also HLA-B44 tumor cell lines expressingMAGE3. The proportion of metastatic melanomas expressing theMAGE3/HLA-1344 antigen should amount to approximately 17% in the Caucasian population, since 24% of individuals carry theHLA-B44 allele and 76% of these tumors express MAGE3.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Atherton, E., Logan, C. J., and Sheppard, R. C. Peptide synthesis. Part 2. Procedures for solid phase synthesis using Nα-fluorenyl-methysoxycarbamylamino-acid on polymide supports. Synthesis of substance P and of acyl carrier protein 65–74 decapeptide.J Chem Soc Lond Perkin Trans 1: 538, 1981
Boon, T., Cerottini, J.-C., Van den Eynde, B., van der Bruggen, P., and Van Pel, A. Tumor antigens recognized by T lymphocytes.Annu Rev Immunol 12: 337–365, 1994
Brasseur, F., Marchand, M., Vanwijck, R., Hérin, M., Lethé, B., Chomez, P., and Boon, T. Human gene MAGE-1, which codes for a tumor rejection antigen, is expressed by some breast tumors.Int J Cancer 52: 839–841, 1992
Brasseur, F., Rimoldi, D., Liénard, D., Letbé, B., Carrel, S., Arienti, F., Suter, L., Vanwijck, R., Bourlond, A., Humblet, Y., Vacca, A., Conese, M., Lahaye, T., Degiovanni, G., Deraemaecker, R., Beauduin, M., Sastre, X., Salamon, E., Dréno, B., Jäger, E., Knuth, A., Chevreau, C., Suciu, S., Lachapelle, M., Pouillart, P., Parmiani, G., Lejeune, F., Cerottini, J.-C., Boon, T., and Marchand, M. Expression of MAGE genes in primary and metastatic cutaneous melanoma.Int J Cancer 63: 375–380, 1995
Brichard, V. G., Herman, J., Van Pel, A., Wildmann, C., Gaugler, B., Wölfel, T., Boon, T., and Lethé, B. A tyrosinase nonapeptide presented by HLA-B44 is recognized on a human melanoma by autologous cytolytic T lymphocytes.Eur J Immunol 26: 224–230, 1996
Burrows, S. R., Misko, I. S., Sculley, T. B., Schmidt, C., and Moss, D. J. An Epstein-Barr virus-specific cytotoxic T-cell epitope present on A- and B-type transformants.J J Virol 64: 3974–3976, 1990
Buseyne, F., McChesney, M., Porrot, F., Kovarik, S., Guy, B., and Rivière, Y. Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: gag epitopes are clustered in three regions of the p24gag protein.J Virol 67: 694–702, 1993
Celis, E., Tsai, V., Crimi, C., DeMars, R., Wentworth, P. A., Chesnut, R. W., Grey, H. M., Sette, A., and Serra, H. M. Induction of antitumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes.Proc Natl Acad Sci USA 91: 2105–2109, 1994
Coulie, P. G., Lehmann, F., Lethé, B., Herman, J., Lurquin, C., Andrawiss, M., and Boon, T. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma.Proc Natl Acad Sci USA 92: 7976–7980, 1995
De Plaen, E., Arden, K., Traversari, C., Gaforio, J. J., Szikora, J.-P, De Smet, C., Brasseur, R., van der Bruggen, P., Lethé, B., Lurquin, C., Brasseur, R., Chomez, P., De Backer, O., Cavenee, W., and Boon, T. Structure, chromosomal localization and expression of twelve genes of theMAGE family.Immunogenetics 40: 360–369, 1994
Del Guercio, M.-E., Sidney, J., Hermanson, G., Perez, C., Grey, H. M., Kubo, R. T., and Sette, A. Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype.J Immunol 154: 685–693, 1995
DiBrino, M., Parker, K. C., Margulies, D. H., Shiloach, J., Turner, R. V., Biddison, W. E., and Coligan, J. E. Identification of the peptide binding motif for HLA-B44, one of the most common HLA-B alleles in the Caucasian population.Biochemistry 34: 10130–10138, 1995
Espevik, T. and Nissen-Meyer, J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes.J Immunol Methods 95: 99–105, 1986
Fleischhauer, K., Kernan, N. A., O'Reilly, R. J., Dupont, B., and Yang, S. Y. Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44.N Engl J Med 323. 1818–1822, 1990
Fleischhauer, K., Kernan, N. A., Dupont, B., and Yang, S. Y. The two major subtypes of HLA-B44 differ for a single amino acid in codon 156.Tissue Antigens 37: 133–137, 1991
Fleischhauer, K., Avila, D., Vilbois, F., Traversari, C., Bordignon, C., and Wallny, H. Characterization of natural peptide ligands for HLA-B*4402 and HLA-B*4403: implications for peptide involvement in allorecognition of a single amino acid change in the HLAB44 heavy chain.Tissue Antigens 44: 311–7317, 1994
Gaugler, B., Van den Eynde, B., van der Bruggen, P., Romero, P., Gaforio, J. J., De Plaen, E., Lethé, B., Brasseur, F., and Boon, T. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes.J Exp Med 179: 921–930, 1994
Gluzman, Y. SV40-transformed simian cells support the replication of early SV40 mutants.Cell 23: 175–182, 1981
Imanishi, T., Akaza, T., Kimura, A., Tokunaga, K., and Gojobori, T. Allele and haplotype frequencies for HLA and complement loci in various ethnic groups. In K. Tsuji, M. Aizawa, and T. Sasazuki (eds.):HLA 1991, Vol 1, XIth International Histocompatibility Workshop and Conference, Oxford University Press, Oxford, 1991
Keever, C. A., Leong, N., Cunningham, I., Copelan, E. A., Avalos, B. R., Klein, J., Kapoor, N., Adams, P. W., Orosz, C. G., Tutschka, P. J., and Baxter-Lowe, L. A. HLA-B44-directed cytotoxic T cells associated with acute graft-versus-host disease following unrelated bone marrow transplantation.Bone Marrow Transplant 14: 137–145, 1994
Khanna, R., Burrows, S. R., Kurilla, M. G., Jacob, C. A., Misko, I. S., Sculley, T. B., Kieff, E., and Moss, D. J. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.J Exp Med 176: 169–176, 1992
Kita, H., Moriyama, T., Kaneko, T., Harase, I., Nomura, M., Miura, H., Nakamura, I., Yazaki, Y., and Imawari, M. HLA-B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein.Hepatology 18: 1039–1044, 1993
Lee, T. D. Distributions of HLA antigens. In J. Lee (ed.):The HLA System. A New Approach, pp. 141–178, Springer, Berlin Heidelberg, 1990
Lehmann, F., Marchand, M., Hainaut, P., Pouillart, P., Sastre, X., Ikeda, H., Boon, T., and Coulie, P. G. Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection.Eur J Immunol 25: 340–347, 1995
Mikamo, S. A novel method for the purification of sheep red cell rosetting lymphocytes.J Immunol Methods 107: 189–196, 1988
Muscatelli, F., Walker, A. P., De Plaen, E., Stafford, A. N., and Monaco, A. P. Isolation and characterisation of a new MAGE gene family in the Xp21.3 region.Proc Natl Acad Sci USA, 92: 4987–4991, 1995
Patard, J.-J., Brasseur, F., Gil-Diez, S., Radvanyi, F., Marchand, M., François, P., Abi Aad, A., Van Cangh, P., Abbou, C. C., Chopin, D., and Boon, T. Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder.Int J Cancer 64: 60–64, 1995
Petersdorf, E. W., Setoda, T., Smith, A. G., and Hansen, J. A. Analysis of HLA-13*44 alleles encoded on extended HLA haplotypes by direct automated sequencing.Tissue Antigens 44: 211–216, 1994
Romani, N., Gruner, S., Brang, D., Kämpgen, E., Lenz, A., Trockenbacher, B., Konwalinka, G., Fritsch, P O., Steinman, R. M., and Schuler, G. Proliferating dendritic cell progenitors in human blood.J Exp Med 180: 83–93, 1994
Russo, V., Traversari, C., Verrecchia, A., Mottolese, M., Natali, P. G., and Bordignon, C.: Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy.Int J Cancer 64: 216–221, 1995
Sallusto, F. and Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α.J Exp Med 179: 1109–1118, 1994
Seed, B. and Aruffo, A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure.Proc Natl Acad Sci USA 84: 3365–3369, 1987
Sidney, J., del Guercio, M.-F., Southwood, S., Engelhard, V. H., Appella, E., Rammensee, H.-G., Falk, K., Rötzschke, O., Takiguchi, M., Kubo, R. T., Grey, H. M., and Sette, A. Several HLA alleles share overlapping peptide specificities.J Immunol 154: 247–259, 1995
Storkus, W. J., Howell, D. N., Salter, R. D., Dawson, J. R., and Cresswell, P. NK susceptibility varies inversely with target cell class I HLA antigen expression.J Immunol 138: 1657–1659, 1987
Traversari, C., van der Bruggen, P., Luescher, I. F., Lurquin, C., Chomez, P., Van Pel, A., De Plaen, E., Amar-Costesec, A., and Boon, T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-Al by cytolytic T lymphocytes directed against tumor antigen MZ2-E.J Exp Med 176: 1453–1457, 1992
Van der Bruggen, P., Bastin, J., Gajewski, T., Coulie, P. G., Boël, P., De Smet, C., Traversari, C., Townsend, A., and Boon, T. 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, 1994
Van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., and Boon, T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.Science 254: 1643–1647, 1991
Weynants, P., Lethé, B., Brasseur, F., Marchand, M., and Boon, T. Expression of MAGE genes by non-small-cell lung carcinomas.Int J Cancer 56: 826–829, 1994
Yao, Z., Keller, E., Scholz, S., McNicholas, A., Volgger, A., and Albert, A. Identification of two major HLA-1344 subtypes and a novel B44 sequence (B*4404).Hum Immunol 42: 54–60, 1995a
Yao, Z., Lattermann, A., Volgger, A., McNicholas, A., Mueller-Eckhardt, G., and Albert, E. A newHLA-B44 subtype,B*4406, differing in exon 2.Immunogenetics 41: 387, 1995b
Yao, Z., Volgger, A., Scholz, S., Bönisch, J., and Albert, E. D. Nucleotide sequence of a novel HLA-B44 subtype (B*4405).Immunogenetics 40: 310, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Herman, J., van der Bruggen, P., Luescher, I.F. et al. A peptide encoded by the human MAGE3 gene and presented by HLA-1344 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3. Immunogenetics 43, 377–383 (1996). https://doi.org/10.1007/BF02199806
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02199806