Abstract
Db-/-xβ2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.
Original language | English |
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Pages (from-to) | 1655-1663 |
Number of pages | 9 |
Journal | British Journal of Cancer |
Volume | 97 |
Issue number | 12 |
DOIs | |
State | Published - 17 Dec 2007 |
Externally published | Yes |
Bibliographical note
Funding Information:The skilful technical assistance of Mrs S Rubinraut in peptide synthesis is greatly appreciated. This study was supported by grants from the Israeli Science Foundation, from the Minerva Foundation, by a research grant from the Lewis Family Charitable Trust (to LE) and by Israel – Korea Research Collaboration Grant from ‘Korean Ministry of Science and Technology’ (to M-S D). LE is the incumbent of the George F Duckwitz chair of cancer research.
Keywords
- Colon cancer
- Cytotoxic T lymphocyte
- Peptides
- Tumour immunity