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

Meriem Belabed, François-Xavier Mauvais, Sophia Maschalidi, Mathieu Kurowska, Nicolas Goudin, Jian-Dong Huang, Alain Fischer, Geneviève Basile, Peter Endert, Fernando E. Sepulveda and Gaël Ménasché ()
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Meriem Belabed: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
François-Xavier Mauvais: Université de Paris, INSERM, U1151, Institut Necker Enfants Malades; Université de Paris; CNRS, UMR8253
Sophia Maschalidi: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
Mathieu Kurowska: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
Nicolas Goudin: Cell Imaging Facility, Université de Paris, Imagine Institute
Jian-Dong Huang: The University of Hong Kong
Alain Fischer: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
Geneviève Basile: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
Peter Endert: Université de Paris, INSERM, U1151, Institut Necker Enfants Malades; Université de Paris; CNRS, UMR8253
Fernando E. Sepulveda: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163
Gaël Ménasché: Laboratory of Molecular basis of altered immune homeostasis, INSERM UMR1163

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15692-0

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