Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4(+) T lymphocytes

MAGE-type genes are expressed by many tumors of different histological type s and not by normal cells, except for male germline cells, which do not exp ress major histocompatibility complex (MHC) molecules. Therefore, the antig ens encoded by MAGE-type genes are strictly tumor specific and common to ma ny tumors. We describe here the identification of the first MAGE-encoded ep itopes presented by histocompatibility leukocyte antigen (HLA) class II mol ecules to CD4(+) T lymphocytes. Monocyte-derived dendritic cells were loade d with a MAGE-3 recombinant protein and used to stimulate autologous CD4(+) T cells. We isolated CD4(+) T cell clones that recognized two different MA GE-3 epitopes, MAGE-3(114-127) and MAGE-3(121-134), both presented by the H LA-DR13 molecule, which is expressed in 20% of Caucasians. The second epito pe is also encoded by MAGE-1, -2, and -6. Our procedure should be applicabl e to other proteins for the identification of new tumor-specific antigens p resented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized w ith proteins or with recombinant viruses carrying entire genes coding for t umor antigens. The use of antigenic peptides presented by class II in addit ion to peptides presented by class I may also improve the efficacy of thera peutic antitumor vaccination.