Transient aggregation of ubiquitinated proteins during dendritic cell maturation
Transient aggregation of ubiquitinated proteins during dendritic cell maturation
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DOI：
10.1038/417177a
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发表时间：
2002-05-09
期刊：
影响因子：
64.8
通讯作者：
Pierre, P
中科院分区：
文献类型：
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作者：
Lelouard, H;Gatti, E;Pierre, P
树突状细胞（DC）是具有启动初级免疫应答的独特能力的抗原呈递细胞（1）。树突状细胞具有显著的分化（成熟）模式，其表现出高度特异性的机制来控制受主要组织相容性复合体（MHC）限制的抗原呈递（2）。MHC I类分子向CD 8（+）细胞毒性T细胞呈递主要来源于胞质蛋白的肽，其被泛素化，然后被蛋白酶体降解（3，4）。在这里，我们表明，在炎症刺激，树突状细胞积累新合成的泛素化蛋白在大的胞质结构。这些结构与许多淀粉样蛋白疾病中观察到的侵袭体和包涵体相似，但不同（5，6）。值得注意的是，这些树突状细胞攻击样诱导结构（DALIS）是短暂的，需要连续的蛋白质合成，不影响泛素-蛋白酶体途径。我们的观察表明，存在一个有组织的优先级的蛋白质降解刺激的DC，这可能是重要的调节MHC I类成熟过程中的介绍。
Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to initiate primary immune responses(1). Dendritic cells have a remarkable pattern of differentiation (maturation) that exhibits highly specific mechanisms to control antigen presentation restricted by major histocompatibility complex (MHC)(2). MHC class I molecules present to CD8(+) cytotoxic T cells peptides that are derived mostly from cytosolic proteins, which are ubiquitinated and then degraded by the proteasome(3,4). Here we show that on inflammatory stimulation, DCs accumulate newly synthesized ubiquitinated proteins in large cytosolic structures. These structures are similar to, but distinct from, aggresomes and inclusion bodies observed in many amyloid diseases(5,6). Notably, these dendritic cell aggresome-like induced structures (DALIS) are transient, require continuous protein synthesis and do not affect the ubiquitin-proteasome pathway. Our observations suggest the existence of an organized prioritization of protein degradation in stimulated DCs, which is probably important for regulating MHC class I presentation during maturation.