Myosin II synergizes with F-actin to promote DNGR-1-dependent cross-presentation of dead cell-associated antigens
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2018-07-10
Date Acceptance
2018-06-08
Citation
Cell Reports, 2018, 24 (2), pp.419-428
ISSN
2211-1247
Publisher
Elsevier
Start Page
419
End Page
428
Journal / Book Title
Cell Reports
Volume
24
Issue
2
Copyright Statement
© 2018 The Francis Crick Institute. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29996102
PII: S2211-1247(18)30948-3
Subjects
C-type lectin
CLEC9A
DNGR-1
actin
actin-binding proteins
dendritic cells
myosin II
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-07-11