Tirosh B, Daniel-Carmi V, Carmon L, Paz A, Lugassy G, Vadai E, Machlenkin A, Bar-Haim E, Do M-S, Ahn I S, Fridkin M, Tzehoval E, Eisenbach L
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Br J Cancer. 2007 Dec 17;97(12):1655-63. doi: 10.1038/sj.bjc.6604061. Epub 2007 Dec 11.
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.
D(b-/-)β2微球蛋白（β2m）基因敲除小鼠转染嵌合HLA-A2.1/D(b)-β2m单链基因（HHD小鼠）是一种有效的生物学工具，可用于评估已知主要组织相容性限制肽肿瘤相关抗原的抗肿瘤细胞毒性T淋巴细胞反应，并筛选潜在的未知新肽。我们利用HHD淋巴细胞鉴定结肠癌过表达基因的免疫显性表位。我们用来自HHD的淋巴细胞筛选了500多种源自结肠癌过表达基因的HLA-A2.1限制肽。这一过程最终鉴定出7种免疫原性肽，其中3种源自“干扰素诱导基因的人1-8D基因”（1-8D）。1-8D基因在新鲜肿瘤样本中显示过表达。这3种1-8D肽在HHD小鼠中既具有抗原性又具有免疫原性。这些肽可诱导细胞毒性T淋巴细胞，在体外能够杀死结肠癌细胞系HCT/HHD，并在体内抑制其生长。所有1-8基因家族共有的一种肽能有效激活正常人细胞毒性T淋巴细胞前体。这些结果突出了1-8D基因及其同源物作为结肠癌潜在免疫显性肿瘤相关抗原的地位。
