A VIRAL INHIBITOR OF PEPTIDE TRANSPORTERS FOR ANTIGEN PRESENTATION
A VIRAL INHIBITOR OF PEPTIDE TRANSPORTERS FOR ANTIGEN PRESENTATION
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DOI：
10.1038/375415a0
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发表时间：
1995-06-01
期刊：
影响因子：
64.8
通讯作者：
YANG, Y
中科院分区：
文献类型：
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作者：
FRUH, K;AHN, K;YANG, Y
细胞毒性T淋巴细胞在T细胞受体介导的I类主要组织相容性复合物分子呈递肽识别后裂解靶细胞（1）。抗原肽通过蛋白酶体在细胞质中产生（2），并通过肽转运蛋白（TAP）转运至内质网（ER）内腔3-6。单纯疱疹病毒（HSV）表达一种胞质蛋白，ICP 47，其似乎通过介导ER中“空”I类分子的保留来干扰这种免疫监视（7，8）。通过在HeLa细胞中在诱导型启动子下表达ICP 47（9），我们表明ICP 47有效地抑制肽转运穿过ER膜，使得新生I类分子不能获得抗原肽。这种抑制作用可通过抑制鼠TAP来克服。此外，我们证明了ICP 47在细胞内与TAP共定位和物理缔合，通过病毒蛋白抑制肽易位表明先前未记录的病毒免疫逃避的潜在机制。
CYTOTOXIC T lymphocytes lyse target cells after T-cell-receptor-mediated recognition of class I major histocompatibility complex molecules presenting peptides(1). Antigenic peptides are generated in the cytoplasm by proteasomes(2) and translocated into the lumen of the endoplasmic reticulum (ER) by peptide transporters (TAP)3-6. Herpes simplex virus (HSV) expresses a cytoplasmic protein, ICP47, which seems to interfere with such immune surveillance by mediating retention of 'empty' class I molecules in the ER(7,8). BY expressing ICP47 in HeLa cells under an inducible promoter(9), we show that ICP47 efficiently inhibits peptide transport across the ER membrane such that nascent class I molecules fail to acquire antigenic peptides. This inhibition was overcome by transfecting murine TAP. Further, we demonstrate that ICP47 colocalizes and physically associates with TAP within the cell, Inhibition of peptide translocation by a viral protein indicates a previously undocumented potential mechanism for viral immune evasion.