TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation.
TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation.
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DOI：
10.1016/j.cell.2014.04.054
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发表时间：
2014-07-31
期刊：
影响因子：
64.5
通讯作者：
Blander JM
中科院分区：
文献类型：
--
作者：
Nair-Gupta P;Baccarini A;Tung N;Seyffer F;Florey O;Huang Y;Banerjee M;Overholtzer M;Roche PA;Tampé R;Brown BD;Amsen D;Whiteheart SW;Blander JM
树突状细胞中MHC I类（MHC-I）递呈的内质网（ER）途径的适应性使得来自被吞噬微生物、感染细胞或肿瘤细胞的肽能够交叉递呈到CD8 T细胞。这些多肽如何与mhc - 1分子相交仍然知之甚少。在这里，我们发现mhc - 1选择性地积累在携带微生物成分的吞噬体中，这些微生物成分参与toll样受体（TLR）信号传导。虽然交叉呈递需要sec22b介导的吞噬体从er -高尔基体中间区（ERGIC）募集肽负载复合物，但这一步骤不依赖于TLR信号，也不传递mhc - 1。相反，mhc - 1是从内体循环室（ERC）募集的，ERC由Rab11a、VAMP3/cellubrevin和VAMP8/endobrevin标记，并拥有大量mhc - 1储备。Rab11a活性与MHC-I一起储存ERC， myd88依赖的TLR信号驱动iκ b激酶（IKK）2介导的吞噬体相关SNAP23的磷酸化。Phospho-SNAP23稳定SNARE复合物，协调erc -吞噬体融合，吞噬体富集erc来源的MHC-I，并随后在感染期间交叉呈现。
Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I. Instead, MHC-I are recruited from an endosomal recycling compartment (ERC), which is marked by Rab11a, VAMP3/cellubrevin, and VAMP8/endobrevin and holds large reserves of MHC-I. While Rab11a activity stocks ERC stores with MHC-I, MyD88-dependent TLR signals drive IκB-kinase (IKK)2-mediated phosphorylation of phagosome-associated SNAP23. Phospho-SNAP23 stabilizes SNARE complexes orchestrating ERC-phagosome fusion, enrichment of phagosomes with ERC-derived MHC-I, and subsequent cross-presentation during infection.
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DOI：
10.1084/jem.20060401
发表时间：
2006-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guiducci C;Ott G;Chan JH;Damon E;Calacsan C;Matray T;Lee KD;Coffman RL;Barrat FJ
通讯作者：
Barrat FJ
影响因子：
64.5
作者：
Suzuki K;Verma IM
通讯作者：
Verma IM
影响因子：
3.3
作者：
Saraste, Jaakko;Goud, Bruno
通讯作者：
Goud, Bruno
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P
影响因子：
64.5
作者：
NEEFJES, JJ;STOLLORZ, V;PLOEGH, HL
通讯作者：
PLOEGH, HL