Zheng P, Guo Y, Niu Q, Levy D E, Dyck J A, Lu S, Sheiman L A, Liu Y
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA.
Nature. 1998 Nov 26;396(6709):373-6. doi: 10.1038/24628.
Fragments of foreign antigens associated with class I molecules of the major histocompatibility complex (MHC) are presented at the cell surface to elicit an immune response. This presentation requires the coordinated expression of several genes contained in the MHC, including those encoding the MHC class I heavy chain, the proteins LMP-2 and LMP-7, which are involved in the proteasomal degradation of cytosolic antigens into peptide fragments that are destined for association with MHC class I molecules, and TAP-1 and TAP-2, which transport these fragments across the membrane of the endoplasmic reticulum at the start of their journey to the cell surface. In many virus-transformed cell lines and spontaneous tumours, these genes are simultaneously repressed. However, the key factor(s) that are essential for their expression and repression have not been identified. Here we report that the proto-oncogene product PML induces expression of LMP-2, LMP-7, TAP-1 and TAP-2 in an MHC-class I-negative, recurrent tumour, leading to the re-expression of cell-surface MHC in tumours and to rejection of the tumours. PML also regulates MHC expression in untransformed fibroblasts. We conclude that malfunction of PML may enable a tumour to evade the immune defence of its host.
与主要组织相容性复合体（MHC）的I类分子相关的外来抗原片段会呈递至细胞表面以引发免疫反应。这种呈递需要MHC中多个基因的协调表达，包括那些编码MHC I类重链的基因、参与将胞质抗原蛋白酶体降解为肽片段（这些肽片段将与MHC I类分子结合）的LMP-2和LMP-7蛋白，以及在这些片段前往细胞表面行程开始时将其转运过内质网膜的TAP-1和TAP-2。在许多病毒转化的细胞系和自发性肿瘤中，这些基因同时受到抑制。然而，尚未确定其表达和抑制所必需的关键因素。在此我们报告，原癌基因产物PML在一个MHC I类阴性的复发性肿瘤中诱导LMP-2、LMP-7、TAP-1和TAP-2的表达，导致肿瘤中细胞表面MHC的重新表达并引发肿瘤排斥。PML还调节未转化成纤维细胞中的MHC表达。我们得出结论，PML功能异常可能使肿瘤逃避宿主的免疫防御。
