首页> 外文期刊>The journal of immunology >Hepatocytes Express Abundant Surface Class I MHC and Efficiently Use Transporter Associated with Antigen Processing, Tapasin, and Low Molecular Weight Polypeptide Proteasome Subunit Components of Antigen Processing and Presentation Pathway
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Hepatocytes Express Abundant Surface Class I MHC and Efficiently Use Transporter Associated with Antigen Processing, Tapasin, and Low Molecular Weight Polypeptide Proteasome Subunit Components of Antigen Processing and Presentation Pathway

机译:肝细胞表达丰富的表面I类MHC,并有效使用与抗原加工,胰蛋白酶和抗原加工和呈递途径的低分子量多肽蛋白酶体亚基组分相关的转运蛋白

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Hepatic expression levels of class I MHC Ags are generally regarded as very low. Because the status of these Ags and their ability to present peptides are important for the understanding of pathogen clearance and tolerogenic properties of the liver, we set out to identify the factors contributing to the reported phenotype. Unexpectedly, we found that the surface densities of Kb and Db on C57BL/6 mouse hepatocytes are nearly as high as on splenocytes, as are the lysate concentrations of mRNA encoding H chain and β2-microglobulin (β2m). In contrast, the components of the peptide-loading pathway are reduced in hepatocytes. Despite the difference in the stoichiometric ratios of H chain/β2m/peptide-loading machineries, both cell types express predominantly thermostable class I and are critically dependent on TAP and tapasin for display of surface Ags. Minor differences in the expression patterns in tapasin?/? background suggest cell specificity in class I assembly. Under immunostimulatory conditions, such as exposure to IFN-γ or Listeria monocytogenes , hepatocytes respond with a vigorous mRNA synthesis of the components of the Ag presentation pathway (up to 10-fold enhancement) but up-regulate H chain and β2m to a lesser degree (2-fold). This type of response should promote rapid influx of newly generated peptides into the endoplasmic reticulum and preferential presentation of foreign/induced Ag by hepatic class I.
机译:通常认为I类MHC Ag的肝表达水平很低。由于这些Ags的状态及其呈递肽的能力对于了解肝脏的病原体清除率和耐受性特性很重要,因此我们着手确定有助于报告表型的因素。出乎意料的是,我们发现C57BL / 6小鼠肝细胞上的Kb和Db的表面密度几乎与脾细胞上的密度相同,编码H链和β2-微球蛋白(β2m)的mRNA的裂解物浓度也差不多。相反,肝细胞中肽加载途径的成分减少。尽管H链/β2m/加载肽的机械的化学计量比有所不同,但两种细胞类型均主要表达I类热稳定性,并严重依赖于TAP和Tapasin来显示表面Ag。 Tapasin?/?中表达模式的微小差异背景提示在I类装配中的细胞特异性。在免疫刺激条件下,例如暴露于IFN-γ或单核细胞增生李斯特菌,肝细胞以强烈的Ag呈递途径成分的mRNA合成反应(最多增强10倍),但在较小程度上上调H链和β2m (<2倍)。这种类型的反应应促进新产生的肽快速流入内质网,并由肝I类优先引入外源/诱导的Ag。

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