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Myosin II Synergizes with F-Actin to Promote DNGR-1-Dependent Cross-Presentation of Dead Cell-Associated Antigens
- Source :
- Cell Reports, Cell Reports, Vol 24, Iss 2, Pp 419-428 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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.<br />Graphical Abstract<br />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<br />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.
- Subjects :
- 0301 basic medicine
CLEC9A
Melanoma, Experimental
macromolecular substances
Article
General Biochemistry, Genetics and Molecular Biology
Cell Line
Motor protein
03 medical and health sciences
Cross-Priming
myosin II
0302 clinical medicine
Phagocytosis
Antigen
Myosin
actin-binding proteins
Animals
Lectins, C-Type
dendritic cells
Actin-binding protein
Antigens
Receptors, Immunologic
lcsh:QH301-705.5
Actin
Myosin Type II
Latex beads
Cell Death
Myosin Heavy Chains
biology
Chemistry
Cross-presentation
Ligand (biochemistry)
Actins
DNGR-1
3. Good health
Cell biology
Mice, Inbred C57BL
C-type lectin
030104 developmental biology
lcsh:Biology (General)
030220 oncology & carcinogenesis
biology.protein
Immunization
actin
Protein Binding
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....fed6b9b4d8a2858b25e26b3b89b9a79a