Analysis of individual specific cytotoxic T lymphocytes for two MAGE-3-derived epitopes presented by HLA-A24

The human MAGE-3 gene encodes tumor-specific antigens that are recognized by cytotoxic T lymphocytes (CTLs) and expressed in a high percentage of various malignant tumors. Of the five MAGE-3-derived CTL epitopes identified to date, two nonapeptides (TFPDLESEF and IMPKAGLLI, designated MAGE-3.A24a an...

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Bibliographic Details
Published in:Japanese journal of clinical oncology 2000-03, Vol.30 (3), p.117-121
Main Authors: Katsura, F, Eura, M, Chikamatsu, K, Oiso, M, Yumoto, E, Ishikawa, T
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Cytotoxicity Tests, Immunologic
Epitopes - analysis
Gene Expression
HLA-A Antigens - analysis
HLA-A24 Antigen
Humans
Neoplasm Proteins - genetics
Neoplasm Proteins - immunology
T-Lymphocytes, Cytotoxic - immunology
Tumor Cells, Cultured - immunology
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Summary:The human MAGE-3 gene encodes tumor-specific antigens that are recognized by cytotoxic T lymphocytes (CTLs) and expressed in a high percentage of various malignant tumors. Of the five MAGE-3-derived CTL epitopes identified to date, two nonapeptides (TFPDLESEF and IMPKAGLLI, designated MAGE-3.A24a and MAGE-3.A24b, respectively) can be expressed on the tumor surface by binding to the HLA-A24 molecule, which is the most frequent HLA class I molecule in Asian populations. To compare the immunogenecities of the two peptides, individual specific CTL lines were generated for each peptide (MAGE-3.A24a and MAGE-3.A24b). Peripheral blood mononuclear cells (PBMCs) from four HLA-A24+ healthy donors were stimulated in vitro with autologous dendritic cells pulsed with MAGE-3.A24a, MAGE-3.A24b or both and were subsequently cultivated with a cytokine combination including interleukin-2. We succeeded in generating peptide-specific CTL lines in two of the four donors. The two CTL lines showed similar cytolytic levels against three MAGE-3+/HLA-A24+ cancer cell lines and also target cells pulsed with the corresponding peptide. Cytolytic activities were blocked by either anti-CD8 or anti-HLA-A24 monoclonal antibodies. The results suggest that MAGE-3.A24a and MAGE-3.A24b peptides have equal potential in inducing MAGE-3-specific and HLA-A24-restricted CTLs.
ISSN:0368-2811
1465-3621
1465-3621
DOI:10.1093/jjco/hyd030