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 be en 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 n aturally process and present endogenous bcr-abl fusion protein to CD4(+) T lymphocytes in the context of HLA class II molecules. To verity this possib ility, the ability of CML-derived dendritic cells (DCs) to present endogeno us bcr-abi fusion protein to bcr-abl fusion peptide-specific CD4+ T-lymphoc yte clones was investigated. The bcr-abl b3a2 peptide-specific and HLA-DRB1 *0901-restricted CD4(+) T-lymphocyte clones produced interferon-gamma in re sponse to stimulation with monocyte-derived DCs from HLA-DRB1*0901(+) patie nts 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 stimula tory activity on bcr-abl-specific CD4(+) T-lymphocyte clones. The response of CD4(+) T-lymphocyte clones to CML-derived mature DCs was higher than tha t to immature DCs and was Inhibited by anti-HLA-DR monoclonal antibody. The se data suggest that CML-derived DCs can process and present endogenous bcr -abi fusion protein to CD4+ T lymphocytes. (C) 2001 by The American Society of Hematology.