TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
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DOI：
10.1038/s41590-021-00903-7
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发表时间：
2021-04
影响因子：
30.5
通讯作者：
Blander JM
中科院分区：
文献类型：
--
作者：
Barbet G;Nair-Gupta P;Schotsaert M;Yeung ST;Moretti J;Seyffer F;Metreveli G;Gardner T;Choi A;Tortorella D;Tampé R;Khanna KM;García-Sastre A;Blander JM
经典的MHC-I递呈依赖于与抗原处理(TAP)相关的转运蛋白(TAP)将胞浆多肽运送到内质网(ER)。病毒禁用TAP来阻止MHC-I呈现，并逃避细胞毒性CD8+T细胞。针对这些病毒启动CD8+T细胞被认为完全依赖于未感染的TAP功能树突状细胞(DC)的交叉呈递。我们发现，即使在所有造血细胞中没有TAP的情况下，也可以在病毒感染期间动员保护性CD8+T细胞。阻断TAP可耗尽MHC-I的内体循环室(ERC)，从而损害Toll样受体调节的交叉呈现。相反，MHC-I聚集在内质网高尔基体中间隔室(ERGIC)，远离Toll样受体的控制，并利用ER-SNARE Sec22b介导的囊泡交通与内化抗原相交，拯救交叉递呈。因此，当DC中经典的MHC-I递呈和ERC依赖的交叉递呈受损时，依赖于ERGIC来源的MHC-I计数器的细胞自主非经典性交叉递呈利用功能障碍来调节CD8+T细胞的启动。
Classic MHC-I presentation relies on shuttling cytosolic peptides into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Viruses disable TAP to block MHC-I presentation and evade cytotoxic CD8+ T cells. Priming CD8+ T cells against these viruses is thought to rely solely on cross-presentation by uninfected TAP-functional dendritic cells (DCs). We found that protective CD8+ T cells could be mobilized during viral infection even when TAP was absent in all hematopoietic cells. TAP blockade depleted the endosomal recycling compartment (ERC) of MHC-I and as such impaired Toll-like receptor-regulated cross-presentation. Instead, MHC-I accumulated in ER-Golgi intermediate compartments (ERGIC), sequestered away from Toll-like receptor control, and coopted ER-SNARE Sec22b-mediated vesicular traffic to intersect with internalized antigen and rescue cross-presentation. Thus, when classic MHC-I presentation and ERC-dependent cross-presentation are impaired in DCs, cell-autonomous non-canonical cross-presentation relying on ERGIC-derived MHC-I counters TAP dysfunction to nevertheless mediate CD8+ T cell priming.
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DOI：
10.1084/jem.20170229
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Alloatti A;Rookhuizen DC;Joannas L;Carpier JM;Iborra S;Magalhaes JG;Yatim N;Kozik P;Sancho D;Albert ML;Amigorena S
通讯作者：
Amigorena S
影响因子：
15.9
作者：
Helft, Julie;Manicassamy, Balaji;Merad, Miriam
通讯作者：
Merad, Miriam
影响因子：
4.4
作者：
Lawand, Myriam;Abramova, Anastasia;van Endert, Peter
通讯作者：
van Endert, Peter
影响因子：
--
作者：
Halenius A;Hengel H
通讯作者：
Hengel H
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P