1. ¹Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
2. ²Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel
3. ³Department of Urology, Barzilai Medical Center, Ashkelon, Israel
4. ⁴Department of Hematology, Barzilai Medical Center, Ashkelon, Israel
5. ⁵School of Life and Food Science, Handong University, Pohang, Korea

Correspondence: Professor L Eisenbach, Department of immunology, Weizmann Institute of Science, Rehovot 76100, Israel. E-mail: lea.eisenbach@weizmann.ac.il

⁶These authors contributed equally to this work.

Received 1 June 2007; Revised 28 September 2007; Accepted 4 October 2007.

Abstract

D^b-/-x2 microglobulin (2m) null mice transgenic for a chimeric HLA-A2.1/D^b-2m 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.