ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum
ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum
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DOI：
10.1038/nature01074
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发表时间：
2002-10-03
期刊：
影响因子：
64.8
通讯作者：
Shastri, N
中科院分区：
文献类型：
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作者：
Serwold, T;Gonzalez, F;Shastri, N
携带CD8抗原的杀伤T细胞检测肿瘤或细胞内病原体的能力需要主要组织相容性复合体(MHC)I类分子在潜在靶细胞表面广泛展示抗原肽(1)。这些多肽来自几乎所有的细胞内蛋白，揭示了外来病原体和突变的存在。细胞如何产生数以千计的不同的多肽，这些多肽被切割成与不同的MHC I类分子结合所需的准确长度，目前尚不清楚。这些多肽被细胞质(4，5)中的蛋白酶体从内源合成的蛋白质中切割，然后被内质网(ER)中的一种未知的氨基肽酶(6-8)修剪。在这里，我们确定ERAAP，与内质网中的抗原处理相关的氨基肽酶。ERAAP具有广泛的底物特异性，其表达被干扰素-γ强烈上调。通过RNA干扰减少ERAAP的表达，可以阻止内质网中MHC I类分子的多肽修剪，并极大地减少细胞表面MHC I类分子的表达。因此，ERAAP是胞浆加工产物和MHC I类分子在细胞表面呈递的最终多肽之间缺失的一环。
The ability of killer T cells carrying the CD8 antigen to detect tumours or intracellular pathogens requires an extensive display of antigenic peptides by major histocompatibility complex (MHC) class I molecules on the surface of potential target cells(1). These peptides are derived from almost all intracellular proteins and reveal the presence of foreign pathogens and mutations. How cells produce thousands of distinct peptides cleaved to the precise lengths required for binding different MHC class I molecules remains unknown(2,3). The peptides are cleaved from endogenously synthesized proteins by the proteasome in the cytoplasm(4,5) and then trimmed by an unknown aminopeptidase in the endoplasmic reticulum (ER)(6-8). Here we identify ERAAP, the aminopeptidase associated with antigen processing in the ER. ERAAP has a broad substrate specificity, and its expression is strongly upregulated by interferon-gamma. Reducing the expression of ERAAP through RNA interference prevents the trimming of peptides for MHC class I molecules in the ER and greatly reduces the expression of MHC class I molecules on the cell surface. Thus, ERAAP is the missing link between the products of cytosolic processing and the final peptides presented by MHC class I molecules on the cell surface.