Identification of a promiscuous T-cell epitope encoded by multiple members of the MAGE family.
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.
Tanzarella
S
S
Telethon Institute of Gene Therapy and Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H.S. Raffaele, Milano, Italy.
Russo
V
V
Lionello
I
I
Dalerba
P
P
Rigatti
D
D
Bordignon
C
C
Traversari
C
C
D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015235:HLA-B Antigens; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C095203:MAGEA6 protein, human; C072012:MAGEB2 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins