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

Summary 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.
Graphical Abstract
Highlights • Myosin II amplifies the activity of the DNGR-1 ligand F-actin • Lack of myosin II in donor cells reduces DNGR-1-dependent cross-presentation • Beads with F-actin and myosin II can target antigens to cDC1 for CD8 T cell priming
Schulz et al. show that dead cells lacking myosin II have a diminished capacity to serve as antigen donors for dendritic cells that express the DNGR-1 receptor. DNGR-1 binds to F-actin exposed on cell corpses, and myosin II organizes actin filaments into bundles that cross-link the receptor more efficiently.