Kinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells
Open Access
- 14 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41467-020-15692-0
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. Kinesin-1 is a motor protein transporting cargo along microtubules. Here the authors show that kinesin-1 is required for antigen cross-presentation and coordinates endosome scission from early endosomes to allow sorting internalized cargoes towards the recycling endosomal or lysosomal compartments.This publication has 38 references indexed in Scilit:
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