Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes

M. Makita, T. Azuma, H. Hamaguchi, H. Niiya, K. Kojima, S. Fujita, M. Tanimoto, M. Harada, M. Yasukawa

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Abstract

Although CD4+ helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4+ T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4+ T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4+ T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4+ T lymphocyte clones produced interferon-γ (IFN-γ) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-γ production by CN4+T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4+ T lymphocytes.

Original languageEnglish
Pages (from-to)2400-2407
Number of pages8
JournalLeukemia
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

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Keywords

  • CD T lymphocytes
  • Dendritic cells
  • Immunotherapy
  • Leukemia
  • Tumor-associated antigens

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Makita, M., Azuma, T., Hamaguchi, H., Niiya, H., Kojima, K., Fujita, S., Tanimoto, M., Harada, M., & Yasukawa, M. (2002). Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes. Leukemia, 16(12), 2400-2407. https://doi.org/10.1038/sj.leu.2402742