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

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  • Sophia Maschalidi

    (INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune System, Imagine Institute
    Université Paris Descartes)

  • Paula Nunes-Hasler

    (University of Geneva)

  • Clarissa R Nascimento

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Ignacio Sallent

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Valérie Lannoy

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Meriem Garfa-Traore

    (Université Paris Descartes
    INSERM US24 Structure Federative de Recherche Necker)

  • Nicolas Cagnard

    (Université Paris Descartes
    INSERM US24 Structure Federative de Recherche Necker)

  • Fernando E. Sepulveda

    (INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune System, Imagine Institute
    Université Paris Descartes)

  • Pablo Vargas

    (Institut Curie, PSL Research University, Centre National de la Recherche Scientifique, UMR 144
    Institut Pierre-Gilles de Genes, PSL Research University)

  • Ana-Maria Lennon-Duménil

    (Institut National de la Santé et de la Recherché Médicale, Unité 932, Institut Curie, PSL Research University)

  • Peter Endert

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Thierry Capiod

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Nicolas Demaurex

    (University of Geneva)

  • Guillaume Darrasse-Jèze

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

  • Bénédicte Manoury

    (Université Paris Descartes
    Institut National de la Santé et de la Recherche Médicale, Unité 1151
    Centre National de la Recherche Scientifique, UMR 8253)

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.

Suggested Citation

  • Sophia Maschalidi & Paula Nunes-Hasler & Clarissa R Nascimento & Ignacio Sallent & Valérie Lannoy & Meriem Garfa-Traore & Nicolas Cagnard & Fernando E. Sepulveda & Pablo Vargas & Ana-Maria Lennon-Dumé, 2017. "UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01601-5
    DOI: 10.1038/s41467-017-01601-5
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