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

• Published in: Nature communications 2020-04, Vol.11 (1), p.1817-1817, Article 1817
• Main Authors: Belabed, Meriem, Mauvais, François-Xavier, Maschalidi, Sophia, Kurowska, Mathieu, Goudin, Nicolas, Huang, Jian-Dong, Fischer, Alain, de Saint Basile, Geneviève, van Endert, Peter, Sepulveda, Fernando E., Ménasché, Gaël
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/31; 14; 14/19; 631/250/21/1293; 631/80/128/1923; 631/80/313; 631/80/642/1776; 64; 64/60; Acids - metabolism; Animals; Antigen presentation; Antigen Presentation - immunology; Antigens; Antigens - metabolism; Antigens, CD - metabolism; Bone Marrow Cells - cytology; CD8 antigen; Cell Proliferation; Cellular Biology; Cleavage; Compartments; Degradation; Dendritic cells; Dendritic Cells - metabolism; Endocytosis; Endosomes; Endosomes - metabolism; Histocompatibility Antigens Class I - metabolism; Humanities and Social Sciences; Immune system; Kinesin; Kinesin - deficiency; Kinesin - metabolism; Life Sciences; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mice, Knockout; Mice, Transgenic; Microtubules; Microtubules - metabolism; Molecular machines; multidisciplinary; Neoplasms - pathology; Ovalbumin - immunology; Protein transport; Protein turnover; Science; Science (multidisciplinary); Solubility; Subcellular Processes; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15692-0

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.