Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines.
Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines.
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发表时间：
1998-08
期刊：
影响因子：
11.2
通讯作者：
A. Johnsen;J. France;M. Sy;C. Harding
中科院分区：
文献类型：
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作者：
A. Johnsen;J. France;M. Sy;C. Harding
肿瘤细胞可以改变参与抗原加工和呈递的蛋白质的表达，使它们能够避免被细胞毒性T细胞识别和消除。在这项研究中，逆转录-PCR用于评估人肿瘤细胞系中I类MHC抗原加工途径的多个组分的mRNA表达，包括几种蛋白酶体亚基，这些蛋白酶体亚基与抗原加工有关，但以前没有在这种情况下进行过检查（例如，低分子量多肽蛋白酶体亚基（LMP）10、蛋白酶体激活剂（PA）28 α和PA 28 β）。在27个细胞系中有9个表现出抗原处理基因表达的缺陷，代表了各种组织学类型。在某些情况下，在MHC内编码的四种基因（TAP 1、TAP 2、LMP 2和LMP 7）以及在MHC外编码的LMP 10的表达中观察到几乎完全的缺陷。这些基因产物的组合缺陷是常见的，并且在9个具有缺陷的细胞系中的5个中发现了LMP 10的显著缺陷。分散位点基因表达缺陷的存在表明，缺陷的基础是一种调控机制，而不是这些基因的突变或缺失。此外，大多数缺陷通过IFN-γ治疗逆转。与这些极端缺陷相反，我们发现肿瘤细胞系中PA 28 α和PA 28 β的表达未改变或仅部分降低。因此，肿瘤可以通过同时下调MHC-I抗原加工途径的多个组分来逃避免疫监视，从而改变肿瘤抗原的加工和呈递。然而，必需的蛋白酶体亚基的表达仍然可以维持。
Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In this study, reverse transcription-PCR was used to assess the expression in human tumor cell lines of mRNA for multiple components of the class I MHC antigen-processing pathway, including several proteasome subunits that have been implicated in antigen processing but have not been previously examined in this context (e.g., low molecular weight polypeptide proteasome subunit (LMP) 10, proteasome activator (PA) 28alpha, and PA28beta). Deficiencies in the expression of antigen-processing genes were demonstrated in 9 of 27 cell lines, representing a variety of histological types. In some cases, virtually complete deficiencies were observed in the expression of the four genes encoded within the MHC (TAP1, TAP2, LMP2, and LMP7), as well as LMP10, which is encoded outside the MHC. Combined deficiencies of these gene products were common, and marked deficiency of LMP10 was found in five of the nine cell lines with deficits. The existence of deficiencies in the expression of genes at dispersed loci suggested that the basis for the deficiencies was a regulatory mechanism, as opposed to mutation or deletion of these genes. Furthermore, most of the deficiencies were reversed by treatment with IFN-gamma. In contrast to such extreme deficiencies, we found unaltered or only partially decreased expression of PA28alpha and PA28beta in tumor cell lines. Thus, tumors may evade immune surveillance by simultaneously down-regulating multiple components of the MHC-I antigen-processing pathway, thereby altering the processing and presentation of tumor antigens. Expression of essential proteasome subunits, however, may still be maintained.