Rotem-Yehudar R, Winograd S, Sela S, Coligan J E, Ehrlich R
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
J Exp Med. 1994 Aug 1;180(2):477-88. doi: 10.1084/jem.180.2.477.
The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H-2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo.
12型腺病毒（Ad12）转化的细胞表面I类主要组织相容性复合体抗原的表达通常非常低，这与该病毒的高致癌性相关。在同时表达内源性H-2基因和微型猪I类基因（PD1）的转基因小鼠的原代胚胎成纤维细胞中，Ad12介导的转化导致所有I类抗原的细胞表面表达受到抑制。尽管PD1和H-2Db的I类mRNA水平与未受病毒转化的细胞中的水平相似，但一组单克隆抗体对新合成的I类分子的识别受损，推测是由于I类分子组装和运输效率低下所致。通过在26℃培养细胞，或在37℃将细胞与I类结合肽共培养，可部分诱导I类表达。对Ad12转化细胞系的TAP1和TAP2转运蛋白基因的稳态mRNA水平分析表明，它们均显著降低，TAP2降低约100倍，TAP1降低5-10倍。通过用TAP2而非TAP1表达构建体稳定转染，在Ad12转化的细胞系中实现了PD1和H-2Db而非H-2Kb表达的重建。从这些数据可以得出结论，Ad12转化细胞中肽转运蛋白基因，尤其是TAP2的表达受抑制，会抑制I类分子的细胞表面表达。未能完全重建H-2Db和H-2Kb表达表明，在控制Ad12转化细胞中I类基因表达方面还涉及其他因素。然而，这些结果表明，肽转运蛋白基因的抑制可能是病毒转化细胞在体内逃避免疫识别的重要机制。
