This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanzarella, S. Articles by Traversari, C. Search for Related Content PubMed PubMed Citation Articles by Tanzarella, S. Articles by Traversari, C.

Identification of a Promiscuous T-Cell Epitope Encoded by Multiple Members of the MAGE Family¹

Telethon Institute of Gene Therapy and Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H. S. Raffaele, 20132 Milano, Italy

One of the major limitations of tumor-specific vaccination is the generation of antigen-loss variants that are able to escape the immune response elicited by a monoantigenic peptide epitope. Here, we report the identification of a new HLA-B*3701-restricted epitope shared by four different members of the MAGE family. Peripheral blood lymphocytes isolated from a melanoma patient were stimulated in vitro with the autologous HLA-negative melanoma line transfected with autologous HLA B*3701 molecule. This protocol led to the induction of tumor-specific, B*3701-restricted CTLs specific for a peptide epitope encoded by codons 127–136 of the gene MAGE-1. The same epitope is also encoded by the homologous region of three other members of the MAGE family, MAGE-2, -3, and -6. Consistent with the notion that the peptide encoded by MAGE-1 codons 127–136 is, indeed, processed from the proteins encoded by all four MAGE family members, the CTLs were able to specifically recognize Cos-7 cells cotransfected with HLA-B*3701 and any of these MAGE genes. Moreover, the CTLs also recognized a MAGE-6-positive melanoma line transfected with the B*3701 molecule. These findings allow the inclusion of a new set of tumor patients into clinical cancer vaccination trials. Furthermore, they suggest that some promiscuous peptide epitopes shared by different members of the MAGE family might be less prone to escape the immune response by generation of MAGE antigen loss variants.

This article has been cited by other articles:

				C. Traversari, S. Marktel, Z. Magnani, P. Mangia, V. Russo, F. Ciceri, C. Bonini, and C. Bordignon The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies Blood, June 1, 2007; 109(11): 4708 - 4715. [Abstract] [Full Text] [PDF]

				F. Curnis, R. Longhi, L. Crippa, A. Cattaneo, E. Dondossola, A. Bachi, and A. Corti Spontaneous Formation of L-Isoaspartate and Gain of Function in Fibronectin J. Biol. Chem., November 24, 2006; 281(47): 36466 - 36476. [Abstract] [Full Text] [PDF]

				L. Sigalotti, E. Fratta, S. Coral, S. Tanzarella, R. Danielli, F. Colizzi, E. Fonsatti, C. Traversari, M. Altomonte, and M. Maio Intratumor Heterogeneity of Cancer/Testis Antigens Expression in Human Cutaneous Melanoma Is Methylation-Regulated and Functionally Reverted by 5-Aza-2'-deoxycytidine Cancer Res., December 15, 2004; 64(24): 9167 - 9171. [Abstract] [Full Text] [PDF]

				D. Atanackovic, N. K. Altorki, E. Stockert, B. Williamson, A. A. Jungbluth, E. Ritter, D. Santiago, C. A. Ferrara, M. Matsuo, A. Selvakumar, et al. Vaccine-Induced CD4+ T Cell Responses to MAGE-3 Protein in Lung Cancer Patients J. Immunol., March 1, 2004; 172(5): 3289 - 3296. [Abstract] [Full Text] [PDF]

				S. Graff-Dubois, O. Faure, D.-A. Gross, P. Alves, A. Scardino, S. Chouaib, F. A. Lemonnier, and K. Kosmatopoulos Generation of CTL Recognizing an HLA-A*0201-Restricted Epitope Shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 Tumor Antigens: Implication in a Broad-Spectrum Tumor Immunotherapy J. Immunol., July 1, 2002; 169(1): 575 - 580. [Abstract] [Full Text] [PDF]

				H. Kobayashi, Y. Song, D. S. B. Hoon, E. Appella, and E. Celis Tumor-reactive T Helper Lymphocytes Recognize a Promiscuous MAGE-A3 Epitope Presented by Various Major Histocompatibility Complex Class II Alleles Cancer Res., June 1, 2001; 61(12): 4773 - 4778. [Abstract] [Full Text] [PDF]

				I. Miyashiro, C. Kuo, K. Huynh, A. Iida, D. Morton, A. Bilchik, A. Giuliano, and D. S.B. Hoon Molecular Strategy for Detecting Metastatic Cancers with Use of Multiple Tumor-specific MAGE-A Genes Clin. Chem., March 1, 2001; 47(3): 505 - 512. [Abstract] [Full Text] [PDF]

				V. Russo, D. Zhou, C. Sartirana, P. Rovere, A. Villa, S. Rossini, C. Traversari, and C. Bordignon Acquisition of intact allogeneic human leukocyte antigen molecules by human dendritic cells Blood, June 1, 2000; 95(11): 3473 - 3477. [Abstract] [Full Text] [PDF]

				V. Russo, S. Tanzarella, P. Dalerba, D. Rigatti, P. Rovere, A. Villa, C. Bordignon, and C. Traversari Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response PNAS, February 29, 2000; 97(5): 2185 - 2190. [Abstract] [Full Text] [PDF]