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Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2007 Apr; Vol. 30 (3), pp. 282-93. - Publication Year :
- 2007
-
Abstract
- Effective tumor vaccine may be required to induce both cytotoxic T lymphocyte (CTL) and CD4+ helper T-cell responses against tumor-associated antigens. CD4+ helper T cells that recognize HLA class II-restricted epitopes play a central role in the initiation and maintenance of antitumor immune responses. The Wilms tumor gene WT1 is overexpressed in both leukemias and solid tumors, and the WT1 protein was demonstrated to be an attractive target antigen for cancer immunotherapy. In this study, we identified a WT1 protein-derived 16-mer peptide, WT1(332)(KRYFKLSHLQMHSRKH), which was restricted with HLA-DRB1*0405, one of the most common HLA class II types in Japanese, as a helper epitope that could elicit WT1-specific CD4+ T-cell responses. We established a WT1(332)-specific CD4+ helper T-cell clone (E04.1), which could respond to both HLA-DRB1*0405-positive, WT1-expressing transformed hematopoietic cells and autologous dendritic cells pulsed with apoptosis-induced WT1-expressing cells, indicating that the WT1(332) was a naturally processed helper epitope. Stimulation of peripheral blood mononuclear cells with both the CTL epitope (WT1(235)) and the helper epitope (WT1(332)) in the presence of WT1(332)-specific TH1-type CD4+ T cell clone strikingly enhanced the induction and the functional activity of WT1(235)-specific CTLs compared with that of peripheral blood mononuclear cells with the WT1(235) alone. These results indicated that a helper epitope, WT1(332) should be useful for improvement of the efficacy of CTL epitope-based cancer vaccine targeting WT1 in the clinical setting.
- Subjects :
- CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
Cancer Vaccines immunology
Epitope Mapping
Epitopes, T-Lymphocyte genetics
Genes, Wilms Tumor
HLA-DRB1 Chains
Humans
Interferon-gamma
Lymphocyte Activation
Oligopeptides genetics
T-Lymphocytes, Cytotoxic immunology
WT1 Proteins chemistry
WT1 Proteins genetics
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte pharmacology
HLA-DR Antigens immunology
Oligopeptides immunology
Oligopeptides pharmacology
T-Lymphocytes, Cytotoxic drug effects
WT1 Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-9557
- Volume :
- 30
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 17414319
- Full Text :
- https://doi.org/10.1097/01.cji.0000211337.91513.94