HLA class II–restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia–derived dendritic cells to CD4+ T lymphocytes

• Published in: Blood Vol. 98; no. 5; pp. 1498 - 1505
• Main Authors: Yasukawa, Masaki, Ohminami, Hideki, Kojima, Kensuke, Hato, Takaaki, Hasegawa, Atsuhiko, Takahashi, Tsuyoshi, Hirai, Hisamaru, Fujita, Shigeru
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.09.2001; The Americain Society of Hematology
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigen Presentation; Antineoplastic agents; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Cell Separation; Clone Cells - immunology; Dendritic Cells - immunology; Flow Cytometry; Fusion Proteins, bcr-abl - immunology; Hematologic and hematopoietic diseases; HLA-DR Antigens - immunology; HLA-DRB1 Chains; Humans; Immunotherapy; Interferon-gamma - biosynthesis; L Cells - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Medical sciences; Membrane Glycoproteins - pharmacology; Mice; Molecular Sequence Data; Monocytes - immunology; Monocytes - pathology; Peptide Fragments - immunology; Perforin; Pharmacology. Drug treatments; Pore Forming Cytotoxic Proteins; Chromosomal aberration; Dendritic cell; Antigen presentation; HLA-System; Cell therapy; Major histocompatibility system; Class II histocompatibility antigen; Malignant hemopathy; Cell subpopulation; Philadelphia chromosome; Myeloproliferative syndrome; Chronic; HLA-A-Locus; Histocompatibility restriction; Antigen presenting cell; Immunotherapy; Chronic myelocytic leukemia; T-Lymphocyte; Abnormal chromosome; Fusion protein; Hybrid gene; Clone
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.5.1498

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-γ 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.