Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation.

Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation.
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在树突状细胞成熟期间,对主要组织相容性复合物(MHC)和MHC II类分子的介绍差异调节。

DOI:
10.1084/jem.20021542
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发表时间:
2003-07-07
影响因子:
15.3
通讯作者:
Mellman, I
Mellman, I
中科院分区:
医学1区
文献类型:
--
作者:
Delamarre, L;Holcombe, H;Mellman, I

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在成熟过程中,树突状细胞(DC)调节其处理和呈递主要组织相容性复合体(MHC)II限制性抗原的能力。在这里,我们表明,介绍外源性抗原的MHC I也受到发展的控制,但在一个时尚显着不同的MHC II。未成熟小鼠骨髓来源的DC内化可溶性卵清蛋白并在细胞内隔离抗原,直到它们接收到诱导交叉呈递的适当信号。此时,肽以蛋白酶体依赖的方式产生,并用于形成出现在质膜上的肽-MHC I复合物。与MHC II不同,这些事件不涉及预先存在的MHC I分子从细胞内隔室到DC表面的显著再分布。此外,在9种已知诱导DC表型成熟和促进MHC II呈递的刺激中,只有两种(CD 40连接、细胞-细胞接触的破坏)激活了MHC I上的交叉呈递。相反,即使在未刺激的未成熟DC中,也发生由内源性胞质抗原形成肽-MHC I复合物。因此,在DC成熟过程中,抗原呈递的MHC I和MHC II途径受到差异调节。
During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II–restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow–derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide–MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell–cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide–MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.
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