Activation by SLAM Family Receptors Contributes to NK Cell Mediated "Missing-Self" Recognition.

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Serval ID
serval:BIB_6562347F8E45
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Activation by SLAM Family Receptors Contributes to NK Cell Mediated "Missing-Self" Recognition.
Journal
PLoS One
Author(s)
Alari-Pahissa E., Grandclément C., Jeevan-Raj B., Leclercq G., Veillette A., Held W.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
11
Number
4
Pages
e0153236
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
Natural Killer (NK) cells attack normal hematopoietic cells that do not express inhibitory MHC class I (MHC-I) molecules, but the ligands that activate NK cells remain incompletely defined. Here we show that the expression of the Signaling Lymphocyte Activation Molecule (SLAM) family members CD48 and Ly9 (CD229) by MHC-I-deficient tumor cells significantly contributes to NK cell activation. When NK cells develop in the presence of T cells or B cells that lack inhibitory MHC-I but express activating CD48 and Ly9 ligands, the NK cells' ability to respond to MHC-I-deficient tumor cells is severely compromised. In this situation, NK cells express normal levels of the corresponding activation receptors 2B4 (CD244) and Ly9 but these receptors are non-functional. This provides a partial explanation for the tolerance of NK cells to MHC-I-deficient cells in vivo. Activating signaling via 2B4 is restored when MHC-I-deficient T cells are removed, indicating that interactions with MHC-I-deficient T cells dominantly, but not permanently, impair the function of the 2B4 NK cell activation receptor. These data identify an important role of SLAM family receptors for NK cell mediated "missing-self" reactivity and suggest that NK cell tolerance in MHC-I mosaic mice is in part explained by an acquired dysfunction of SLAM family receptors.
Pubmed
Web of science
Open Access
Yes
Create date
23/04/2016 16:54
Last modification date
20/08/2019 14:21
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