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2018 ; 24
(2
): 419-428
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Myosin II Synergizes with F-Actin to Promote DNGR-1-Dependent Cross-Presentation
of Dead Cell-Associated Antigens
#MMPMID29996102
Schulz O
; Han? P
; Böttcher JP
; Hoogeboom R
; Diebold SS
; Tolar P
; Reis e Sousa C
Cell Rep
2018[Jul]; 24
(2
): 419-428
PMID29996102
show ga
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.