HLA class II–restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia–derived dendritic cells to CD4+ T lymphocytes
2001
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.
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