UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells

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Maschalidi, Sophia | Nunes-Hasler, Paula | Nascimento, Clarissa, R | Sallent, Ignacio | Lannoy, Valérie | Garfa-Traore, Meriem | Cagnard, Nicolas | Sepulveda, Fernando, E | Vargas, Pablo | Lennon-Duménil, Ana-Maria | van Endert, Peter | Capiod, Thierry | Demaurex, Nicolas | Darrasse-Jèze, Guillaume | Manoury, Bénédicte

Edité par CCSD ; Nature Publishing Group -

International audience. Abstract 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-Ca 2+ -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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