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Blood, 1 September 2001, Vol. 98, No. 5, pp. 1498-1505
IMMUNOBIOLOGY
HLA class II-restricted antigen presentation of endogenous
bcr-abl fusion protein by chronic myelogenous leukemia-derived
dendritic cells to CD4+ T lymphocytes
Masaki Yasukawa,
Hideki Ohminami,
Kensuke Kojima,
Takaaki Hato,
Atsuhiko Hasegawa,
Tsuyoshi Takahashi,
Hisamaru Hirai, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime
University School of Medicine, Ehime, Japan; the Second Department of
Internal Medicine, Okayama University School of Medicine, Okayama,
Japan; and Department of Hematology and Oncology, Tokyo Graduate
Medical School, University of Tokyo, Tokyo, Japan.
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- 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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