T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.
Science
; 355(6332): 1428-1433, 2017 03 31.
Article
em En
| MEDLINE
| ID: mdl-28280247
ABSTRACT
Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Antígenos CD28
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article