'1-8 Interferon inducible gene family': Putative colon carcinoma-associated antigens

B. Tirosh, V. Daniel-Carmi, L. Carmon, A. Paz, G. Lugassy, E. Vadai, A. Machlenkin, E. Bar-Haim, M. S. Do, I. S. Ahn, M. Fridkin, E. Tzehoval, L. Eisenbach

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 languageEnglish
Pages (from-to)1655-1663
Number of pages9
JournalBritish Journal of Cancer
Volume97
Issue number12
DOIs
StatePublished - 17 Dec 2007
Externally publishedYes

Keywords

  • Colon cancer
  • Cytotoxic T lymphocyte
  • Peptides
  • Tumour immunity

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