Identification of a promiscuous T-cell epitope encoded by multiple membersof the MAGE family

One of the major limitations of tumor-specific vaccination is the generatio n of antigen-loss variants that are able to escape the immune response elic ited 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 pati ent were stimulated in vitro with the autologous HLA-negative melanoma line transfected with autologous ALA 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 IMAGE-I. The same epitope is also encoded by,the homologous region of three other members of the MAGE fa mily, MAGE-2, -3, and -6. Consistent with the notion that the peptide encod ed by MAGE-1, codons 127-136 is, indeed, processed from the proteins encode d by all four MAGE family members, the CTLs were able to specifically recog nize 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 transfe cted 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 me mbers of the MAGE family might be less prone to escape the immune response by generation of MAGE antigen loss variants.