Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets
Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets
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DOI：
10.1002/eji.200425032
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Niedermann, G
中科院分区：
文献类型：
--
作者：
Nil, A;Firat, E;Niedermann, G
迄今为止，分离的胸腺基质亚群中管家和/或免疫蛋白酶体的表达尚未得到分析，但可能对阳性和阴性胸腺选择过程中 MHC I 类分子呈现的自肽库产生重要影响。在这里，我们确定了正向和负向选择基质子集中管家和免疫蛋白酶体 β 亚基以及 PA28 的表达。正向选择的皮质胸腺上皮细胞 (cTEC) 仅表达管家功能，但不表达免疫蛋白酶体 β 亚基 mRNA 和蛋白质。然而，通过感染单核细胞增生李斯特氏菌或注射 IFN-γ，可以在 cTEC 中诱导免疫蛋白酶体 β 亚基。在包括髓质上皮细胞和树突状细胞在内的负选择基质中，管家β亚基蛋白的不完整和低表达，但免疫蛋白酶体β亚基蛋白的高和完整表达表明缺乏适当的管家蛋白酶体和免疫蛋白酶体占优势。如基因敲除 (KO) 小鼠所示，负选择基质中免疫蛋白酶体 β 亚基的表达不依赖于 IFN-γ 受体。 LMP2 的缺失改变了 KO 小鼠中 MHC I 类限制性转基因 P14 TCR 的胸腺选择。数据表明负选择可能主要涉及免疫蛋白酶体肽库，而外周感染可能影响正选择涉及的肽库。
The expression of housekeeping and/or immunoproteasomes in isolated thymic stroma subsets has so far not been analyzed but may have important consequences for self peptide repertoires presented by MHC class I molecules during positive and negative thymic selection. Here we determined the expression of housekeeping and immunoproteasome beta subunits and of PA28 in positively and negatively selecting stroma subsets. Positively selecting cortical thymic epithelial cells (cTEC) expressed only housekeeping but no immunoproteasome beta subunit mRNA and proteins. However, immunoproteasome beta subunits could be induced in cTEC by infection with Listeria monocytogenes or injection of IFN-gamma. In negatively selecting stroma including medullary epithelial cells and dendritic cells, incomplete and low representation of housekeeping beta subunit proteins but high and complete expression of immunoproteasome beta subunit proteins suggests absence of proper housekeeping proteasomes and predominance of immunoproteasomes. Expression of immunoproteasome beta subunits in negatively selecting stroma was independent of IFN-gamma receptor as shown in knockout (KO) mice. Absence of LMP2 altered thymic selection of the MHC class I-restricted transgenic P14 TCR in KO mice. The data suggest that negative selection may primarily involve immunoproteasome peptide repertoires and that peripheral infection may influence peptide repertoires involved in positive selection.