A MAGE-A3 peptide presented by HLA-DP4 is recognized on tumor cells by CD4+ cytolytic T lymphocytes.
Antigens encoded by MAGE-A3 and recognized by T cells are interesting targets for tumor immunotherapy because they are strictly tumor specific and shared by many tumors of various histological types. A number of MAGE-A3 antigenic peptides presented by HLA class I molecules have been used in clinical trials, and regressions of melanoma metastasis have been observed. We report here the identification of a MAGE-A3 epitope, TQHFVQENYLEY, presented to CD4+ T lymphocytes by HLA-DP4 molecules, which are expressed in approximately 76% of Caucasians. This new epitope may be useful both for therapeutic vaccination and for the evaluation of the immune response in cancer patients. Interest ingly, the CD4+ T cells lysed HLA-DP4 tumor cells expressing MAGE-A3, indicating that this epitope, in contrast to other class-II MAGE-A3 epitopes, is presented at the surface of tumor cells. The study of this disparity in the presentation of two epitopes from the same protein may lead to a better understanding of the endogenous class II presentation pathway.
Schultz
E S
ES
Ludwig Institute for Cancer Research, Brussels, Belgium.
Lethé
B
B
Cambiaso
C L
CL
Van Snick
J
J
Chaux
P
P
Corthals
J
J
Heirman
C
C
Thielemans
K
K
Boon
T
T
van der Bruggen
P
P
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006801:Humans; D008545:Melanoma / Q000276:immunology; D009363:Neoplasm Proteins; D018411:Spodoptera / Q000378:metabolism / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins