'1-8 interferon inducible gene family': putative colon carcinoma-associated antigens.
D(b-/-)xbeta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA-A2.1/D(b)-beta2m 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.
Tirosh
B
B
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Daniel-Carmi
V
V
Carmon
L
L
Paz
A
A
Lugassy
G
G
Vadai
E
E
Machlenkin
A
A
Bar-Haim
E
E
Do
M-S
MS
Ahn
I S
IS
Fridkin
M
M
Tzehoval
E
E
Eisenbach
L
L
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D016056:Immunodominant Epitopes; D007372:Interferons / Q000737:chemistry* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015295:Antigens, Tumor-Associated, Carbohydrate; C080081:IFITM2 protein, human; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D010455:Peptides; D007372:Interferons