Matsui M, Machida S, Tomiyama H, Takiguchi M, Akatsuka T
Department of Microbiology, Saitama Medical School, Moroyama-Cho, Iruma-Gun, Saitama 350-0495, Japan.
Biochem Biophys Res Commun. 2001 Jul 13;285(2):508-17. doi: 10.1006/bbrc.2001.5166.
A hepatoma cell line, Hep G2, reveals the diminished HLA class I surface expression and the reduced expression of LMP2, LMP7, and tapasin transcripts, suggesting that the reduced expression of these transcripts may be associated with the low expression of HLA class I molecules. Introduction of tapasin gene dramatically up-regulates the surface expression of HLA class I molecules on Hep G2 cells, and unexpectedly, enhances the expression of LMP2 and LMP7 transcripts as well. Unlike Hep G2, these tapasin-transfected Hep G2 cells are recognized by allo-specific CTL. However, the transfectant is unable to endogenously present an HIV envelope peptide to an HIV-specific CTL clone, suggesting that a proteasome-independent antigen processing pathway exists and still remains defective in the transfectant. These data may provide significant evidence that the nonproteasomal antigen processing pathway as well as the proteasomal pathway may be impaired in tumor cells to escape immune surveillance performed by CTL.
一种肝癌细胞系Hep G2显示出HLA I类分子表面表达减少以及LMP2、LMP7和塔帕辛(tapasin)转录本表达降低,这表明这些转录本表达的减少可能与HLA I类分子的低表达相关。引入塔帕辛基因可显著上调Hep G2细胞上HLA I类分子的表面表达,并且出乎意料的是,还增强了LMP2和LMP7转录本的表达。与Hep G2不同,这些转染了塔帕辛的Hep G2细胞可被同种异体特异性CTL识别。然而,该转染体无法将HIV包膜肽内源性呈递给HIV特异性CTL克隆,这表明存在一种不依赖蛋白酶体的抗原加工途径,并且该转染体中该途径仍然存在缺陷。这些数据可能提供重要证据,表明非蛋白酶体抗原加工途径以及蛋白酶体途径在肿瘤细胞中可能受损,从而逃避CTL执行的免疫监视。