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Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
by
Schlums, Heinrich
, Westerberg, Lisa S
, Sondergaard, Jonas N
, Wagner, Arnika K
, Hoglund, Petter
, Rota, Giorgia
, Alici, Evren
, Schmied, Laurent
, Mohammad, Dara K
, Guarda, Greta
, Giovanna Perinetti Casoni
, Chrobok, Michael
, Bryceson, Yenan T
, Luu, Thuy T
, Mayer, Corinna
, Meinke, Stephan
, Singh, Sunitha B
, Truong, Hieu M
, Saeed, Mezida B
, Kadri, Nadir
in
Actin
/ Gene regulation
/ Histocompatibility antigen H-2
/ Immunological tolerance
/ Immunology
/ Killer cell immunoglobulin-like receptors
/ Localization
/ Ly-49 antigen
/ Major histocompatibility complex
/ Natural killer cells
/ Pattern formation
/ Phosphorylation
/ Self
/ SHP-1 protein
/ SLP-76 protein
/ Syk protein
/ Transcription
/ ZAP-70 protein
2022
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Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
by
Schlums, Heinrich
, Westerberg, Lisa S
, Sondergaard, Jonas N
, Wagner, Arnika K
, Hoglund, Petter
, Rota, Giorgia
, Alici, Evren
, Schmied, Laurent
, Mohammad, Dara K
, Guarda, Greta
, Giovanna Perinetti Casoni
, Chrobok, Michael
, Bryceson, Yenan T
, Luu, Thuy T
, Mayer, Corinna
, Meinke, Stephan
, Singh, Sunitha B
, Truong, Hieu M
, Saeed, Mezida B
, Kadri, Nadir
in
Actin
/ Gene regulation
/ Histocompatibility antigen H-2
/ Immunological tolerance
/ Immunology
/ Killer cell immunoglobulin-like receptors
/ Localization
/ Ly-49 antigen
/ Major histocompatibility complex
/ Natural killer cells
/ Pattern formation
/ Phosphorylation
/ Self
/ SHP-1 protein
/ SLP-76 protein
/ Syk protein
/ Transcription
/ ZAP-70 protein
2022
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Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
by
Schlums, Heinrich
, Westerberg, Lisa S
, Sondergaard, Jonas N
, Wagner, Arnika K
, Hoglund, Petter
, Rota, Giorgia
, Alici, Evren
, Schmied, Laurent
, Mohammad, Dara K
, Guarda, Greta
, Giovanna Perinetti Casoni
, Chrobok, Michael
, Bryceson, Yenan T
, Luu, Thuy T
, Mayer, Corinna
, Meinke, Stephan
, Singh, Sunitha B
, Truong, Hieu M
, Saeed, Mezida B
, Kadri, Nadir
in
Actin
/ Gene regulation
/ Histocompatibility antigen H-2
/ Immunological tolerance
/ Immunology
/ Killer cell immunoglobulin-like receptors
/ Localization
/ Ly-49 antigen
/ Major histocompatibility complex
/ Natural killer cells
/ Pattern formation
/ Phosphorylation
/ Self
/ SHP-1 protein
/ SLP-76 protein
/ Syk protein
/ Transcription
/ ZAP-70 protein
2022
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Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
Paper
Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
2022
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Overview
Signaling via inhibitory KIR/Ly49 receptors preserves natural killer (NK) cell self-tolerance but also conveys NK cell reactivity towards MHC class-I low target cells in an education process. Here, we demonstrate that mouse NK cell education by H-2Dd regulates transcription of several genes in Ly49A+ NK cells including Ptpn6, encoding the phosphatase SHP-1. SHP-1 was highly expressed in uneducated NK cells, in which knock-out of Ptpn6 increased responsiveness. Following NKp46 triggering of uneducated NK cells, a higher synaptic abundance of phosphorylated SHP-1 was found relative to educated NK cells, concomitant with reduced phosphorylation of several signaling molecules, including PLC-y2, SLP-76, ZAP70/Syk and ERK1/2. SHP-1 overlapped extensively with F-actin and SLP-76 in the uneducated activating synapse of Ly49A+ NK cells, whereas a greater association between Ly49A and SHP-1 was observed in educated NK cells. Thus, our results indicate that in addition to transcriptional regulation, a distinct SHP-1 patterning in NK cell activating synapses can determine their tolerance. Competing Interest Statement The authors have declared no competing interest.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
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