Myosin II Synergizes with F-Actin to Promote DNGR-1-Dependent Cross-Presentation of Dead Cell-Associated Antigens

Cell Rep. 2018 Jul 10;24(2):419-428. doi: 10.1016/j.celrep.2018.06.038.


Conventional type 1 DCs (cDC1s) excel at cross-presentation of dead cell-associated antigens partly because they express DNGR-1, a receptor that recognizes exposed actin filaments on dead cells. In vitro polymerized F-actin can be used as a synthetic ligand for DNGR-1. However, cellular F-actin is decorated with actin-binding proteins, which could affect DNGR-1 recognition. Here, we demonstrate that myosin II, an F-actin-associated motor protein, greatly potentiates the binding of DNGR-1 to F-actin. Latex beads coated with F-actin and myosin II are taken up by DNGR-1+ cDC1s, and antigen associated with those beads is efficiently cross-presented to CD8+ T cells. Myosin II-deficient necrotic cells are impaired in their ability to stimulate DNGR-1 or to serve as substrates for cDC1 cross-presentation to CD8+ T cells. These results provide insights into the nature of the DNGR-1 ligand and have implications for understanding immune responses to cell-associated antigens and for vaccine design.

Keywords: C-type lectin; CLEC9A; DNGR-1; actin; actin-binding proteins; dendritic cells; myosin II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Antigens / metabolism*
  • Cell Death
  • Cell Line
  • Cross-Priming / immunology*
  • Immunization
  • Lectins, C-Type / metabolism*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Myosin Heavy Chains / metabolism
  • Myosin Type II / metabolism*
  • Phagocytosis
  • Protein Binding
  • Receptors, Immunologic / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology


  • Actins
  • Antigens
  • Clec9a protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Myosin Type II
  • Myosin Heavy Chains