HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes.
Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes in the context of HLA class II molecules. To verify this possibility, the ability of CML-derived dendritic cells (DCs) to present endogenous bcr-abl fusion protein to bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones was investigated. The bcr-abl b3a2 peptide-specific and HLA-DRB1*0901-restricted CD4+ T-lymphocyte clones produced interferon-gamma in response to stimulation with monocyte-derived DCs from HLA-DRB1*0901+ patients with b3a2 type CML. In contrast, DCs from patients with HLA-DRB1*0901- or b2a2 type CML and those from healthy individuals did not exert stimulatory activity on bcr-abl-specific CD4+ T-lymphocyte clones. The response of CD4+ T-lymphocyte clones to CML-derived mature DCs was higher than that to immature DCs and was inhibited by anti-HLA-DR monoclonal antibody. These data suggest that CML-derived DCs can process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes.
Yasukawa
M
M
First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan. yasukawa@m.ehime-u.ac.jp
Ohminami
H
H
Kojima
K
K
Hato
T
T
Hasegawa
A
A
Takahashi
T
T
Hirai
H
H
Fujita
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002999:Clone Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007739:L Cells / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma; D016044:Fusion Proteins, bcr-abl