Restriction of PD-1 function by
Animals
Autoimmunity
B7-1 Antigen
/ genetics
B7-H1 Antigen
/ metabolism
CD28 Antigens
/ metabolism
Dendritic Cells
/ immunology
Gene Knock-In Techniques
Humans
Immunotherapy
Lymphocyte Activation
Mice
Mice, Mutant Strains
Neoplasms
/ immunology
Programmed Cell Death 1 Receptor
/ metabolism
Protein Binding
T-Lymphocytes
/ immunology
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
10 05 2019
10 05 2019
Historique:
received:
17
10
2018
accepted:
05
04
2019
pubmed:
20
4
2019
medline:
18
12
2019
entrez:
20
4
2019
Statut:
ppublish
Résumé
Targeted blockade of PD-1 with immune checkpoint inhibitors can activate T cells to destroy tumors. PD-1 is believed to function mainly at the effector, but not in the activation, phase of T cell responses, yet how PD-1 function is restricted at the activation stage is currently unknown. Here we demonstrate that CD80 interacts with PD-L1 in cis on antigen-presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 cannot engage PD-1 to inhibit T cell activation when APCs express substantial amounts of CD80. In knock-in mice in which
Identifiants
pubmed: 31000591
pii: science.aav7062
doi: 10.1126/science.aav7062
doi:
Substances chimiques
B7-1 Antigen
0
B7-H1 Antigen
0
CD28 Antigens
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
558-566Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.