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 language | English |
|---|---|
| Pages (from-to) | 2400-2407 |
| Number of pages | 8 |
| Journal | Leukemia |
| Volume | 16 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2002 |
Fingerprint
Keywords
- CD T lymphocytes
- Dendritic cells
- Immunotherapy
- Leukemia
- Tumor-associated antigens
ASJC Scopus subject areas
- Hematology
- Cancer Research
Cite this
Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes. / Makita, M.; Azuma, T.; Hamaguchi, H.; Niiya, H.; Kojima, K.; Fujita, S.; Tanimoto, M.; Harada, M.; Yasukawa, M.
In: Leukemia, Vol. 16, No. 12, 01.12.2002, p. 2400-2407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes
AU - Makita, M.
AU - Azuma, T.
AU - Hamaguchi, H.
AU - Niiya, H.
AU - Kojima, K.
AU - Fujita, S.
AU - Tanimoto, M.
AU - Harada, M.
AU - Yasukawa, M.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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.
AB - 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.
KW - CD T lymphocytes
KW - Dendritic cells
KW - Immunotherapy
KW - Leukemia
KW - Tumor-associated antigens
UR - http://www.scopus.com/inward/record.url?scp=0036937082&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036937082&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2402742
DO - 10.1038/sj.leu.2402742
M3 - Article
C2 - 12454745
AN - SCOPUS:0036937082
VL - 16
SP - 2400
EP - 2407
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 12
ER -