1. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells.
- Author
-
Maschalidi S, Nunes-Hasler P, Nascimento CR, Sallent I, Lannoy V, Garfa-Traore M, Cagnard N, Sepulveda FE, Vargas P, Lennon-Duménil AM, van Endert P, Capiod T, Demaurex N, Darrasse-Jèze G, and Manoury B more...
- Subjects
- Animals, Antigens immunology, Antigens metabolism, Cells, Cultured, Cross-Priming, Dendritic Cells metabolism, Endoplasmic Reticulum metabolism, Female, Humans, Male, Membrane Transport Proteins genetics, Membrane Transport Proteins immunology, Mice, Mice, Inbred C57BL, Protein Binding, Stromal Interaction Molecule 1 genetics, Stromal Interaction Molecule 1 immunology, Antigen Presentation, Calcium metabolism, Dendritic Cells immunology, Membrane Transport Proteins metabolism, Stromal Interaction Molecule 1 metabolism
- 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-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. more...- Published
- 2017
- Full Text
- View/download PDF