Cutting edge: Neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein
Cutting edge: Neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein
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DOI：
10.4049/jimmunol.167.9.4801
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发表时间：
2001-11-01
影响因子：
4.4
通讯作者：
Groettrup, M
中科院分区：
文献类型：
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作者：
Khan, S;de Giuli, R;Groettrup, M
ctl识别肽表位，这些肽表位是由蛋白酶体蛋白水解产生的，并呈现在MHC I类分子上。根据缺陷核糖体产物（DRIP）假说，表位来源于新合成的多肽，这些多肽在翻译后不久就会被降解。DRIP假说将解释表位是如何从长寿命的蛋白质中产生的。我们研究了淋巴细胞性脉络丛脑膜炎病毒核蛋白的免疫优势表位NP118是否需要新合成，其半衰期为bb30天。在四环素调控的转染物中终止核蛋白生物合成两天后，NP118表位的呈现停止。这表明NP118表位是由新合成的核蛋白产生的，而不是来自细胞中长期存在的核蛋白库。因此，淋巴细胞性脉络丛脑膜炎病毒核蛋白是DRIP假说的主要预测，即新合成的需要，被证明是正确的第一个底物。
CTLs recognize peptide epitopes which are proteolytically generated by the proteasome and presented on MHC class I molecules. According to the defective ribosomal product (DRIP) hypothesis, epitopes originate from newly synthesized polypeptides which are degraded shortly after their translation. The DRIP hypothesis would explain how epitopes can be generated from long-lived proteins. We examined whether neosynthesis is required for presentation of the immunodominant epitope NP118 of the lymphocytic choriomeningitis virus nucleoprotein, which has a half-life of >3 days. Two days after nucleoprotein biosynthesis was terminated in a tetracycline-regulated transfectant, the presentation of the NP118 epitope ceased. This indicates that NP118 epitopes are generated from newly synthesized nucleoproteins rather than from the long-lived pool of nucleoproteins in the cell. Therefore, the lymphocytic choriomeningitis virus nucleoprotein is the first substrate for which a major prediction of the DRIP hypothesis, namely the requirement for neosynthesis, is shown to hold true.