Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes.
Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.
Makita
M
M
First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Azuma
T
T
Hamaguchi
H
H
Niiya
H
H
Kojima
K
K
Fujita
S
S
Tanimoto
M
M
Harada
M
M
Yasukawa
M
M
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D009336:Necrosis; D015513:Oncogene Proteins / Q000276:immunology*; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; C104001:DEK-CAN fusion protein, recombinant; D006684:HLA-DR Antigens; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D016044:Fusion Proteins, bcr-abl