期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01601-5
关键词
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资金
- ANR [ANR 2010 MIDI 008 01, ANR-14-CE11-0014]
- FRM [DEQ20130326539]
- Swiss National Foundation [31003A-149566]
- ARC
- La Ligue Ph.D. fellowships
- ARC Foundation [PJA 20141201668]
- Sir Jules Thorn Overseas Charitable Trust
- Agence Nationale de la Recherche (ANR) [ANR-14-CE11-0014] Funding Source: Agence Nationale de la Recherche (ANR)
- Swiss National Science Foundation (SNF) [31003A_149566] Funding Source: Swiss National Science Foundation (SNF)
Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8+ T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca2+-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice. Here, we show that UNC93B1 interacts with the calcium sensor STIM1 in the endoplasmic reticulum, a critical step for STIM1 oligomerization and activation. Expression of a constitutively active STIM1 mutant, which no longer binds UNC93B1, restores antigen degradation and cross-presentation in 3d-mutated DCs. Furthermore, ablation of STIM1 in mouse and human cells leads to a decrease in cross-presentation. Our data indicate that the UNC93B1 and STIM1 cooperation is important for calcium flux and antigen cross-presentation in DCs.
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