MHC class I antigen presentation of DRiP-derived peptides from a model antigen is not dependent on the AAA ATPase p97.
MHC class I antigen presentation of DRiP-derived peptides from a model antigen is not dependent on the AAA ATPase p97.
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DOI：
10.1371/journal.pone.0067796
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dolan BP
中科院分区：
文献类型：
--
作者：
Palmer AL;Dolan BP
CD8+T细胞负责杀死体内被感染或致癌转化的细胞。为了做到这一点，效应CD8+T细胞必须识别它们与靶细胞直接呈递的MHC I类分子结合的同源抗原肽。由于抗原呈递的快速性，人们认为抗原肽是由一组新合成的蛋白质衍生而来的，这些蛋白质在合成后几乎立即被降解，被称为缺陷核糖体产物或液滴。我们最近报道了一种生物检测方法，该方法可以将水滴底物的抗原提呈与其他形式的快速降解蛋白质区分开来，并发现多聚泛素链的拆解可能是有效的水滴提呈所必需的。AAA ATPase p97蛋白是抗原在MHC-I类分子上高效交叉递呈所必需的，在从内质网中提取错误折叠的蛋白质方面起着重要作用。在这里，我们发现，尽管我们观察到p97抑制增加了细胞中多泛素化蛋白的水平，但基因消融或化学抑制p97并没有在很大程度上减少滴状抗原提呈，也没有改变细胞表面MHC I类分子的水平。这些数据表明，仅抑制多泛素链的拆解不足以消除滴状递呈。
CD8+ T cells are responsible for killing cells of the body that have become infected or oncogenically transformed. In order to do so, effector CD8+ T cells must recognize their cognate antigenic peptide bound to a MHC class I molecule that has been directly presented by the target cell. Due to the rapid nature of antigen presentation, it is believed that antigenic peptides are derived from a subset of newly synthesized proteins which are degraded almost immediately following synthesis and termed Defective Ribosomal Products or DRiPs. We have recently reported on a bioassay which can distinguish antigen presentation of DRiP substrates from other forms of rapidly degraded proteins and found that poly-ubiquitin chain disassembly may be necessary for efficient DRiP presentation. The AAA ATPase p97 protein is necessary for efficient cross-presentation of antigens on MHC class I molecules and plays an important role in extracting mis-folded proteins from the endoplasmic reticulum. Here, we find that genetic ablation or chemical inhibition of p97 does not diminish DRiP antigen presentation to any great extent nor does it alter the levels of MHC class I molecules on the cell surface, despite our observations that p97 inhibition increased the levels of poly-ubiquitinated proteins in the cell. These data demonstrate that inhibiting poly-ubiquitin chain disassembly alone is insufficient to abolish DRiP presentation.
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