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Kinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells

Abstract : Dendritic cells (DCs) constitute a specialized population of immune cells that present exogenous antigen (Ag) on major histocompatibility complex (MHC) class I molecules to initiate CD8 + T cell responses against pathogens and tumours. Although cross-presentation depends critically on the trafficking of Ag-containing intracellular vesicular compartments, the molecular machinery that regulates vesicular transport is incompletely understood. Here, we demonstrate that mice lacking Kif5b (the heavy chain of kinesin-1) in their DCs exhibit a major impairment in cross-presentation and thus a poor in vivo anti-tumour response. We find that kinesin-1 critically regulates antigen cross-presentation in DCs, by controlling Ag degradation, the endosomal pH, and MHC-I recycling. Mechanistically, kinesin-1 appears to regulate early endosome maturation by allowing the scission of endosomal tubulations. Our results highlight kinesin-1's role as a molecular checkpoint that modulates the balance between antigen degradation and cross-presentation.
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Submitted on : Thursday, May 28, 2020 - 4:09:37 PM
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Meriem Belabed, François-Xavier Mauvais, Sophia Maschalidi, Mathieu Kurowska, Nicolas Goudin, et al.. Kinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.1817. ⟨10.1038/s41467-020-15692-0⟩. ⟨inserm-02641196⟩

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