| RRC ID |
17572
|
| 著者 |
Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T.
|
| タイトル |
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
|
| ジャーナル |
J Exp Med
|
| Abstract |
Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1-mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain-containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1-TCR colocalization within microclusters is required for efficient PD-1-mediated suppression. This inhibitory mechanism also functions in PD-1(hi) T cells generated in vivo and can be overridden by a neutralizing anti-PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.
|
| 巻・号 |
209(6)
|
| ページ |
1201-17
|
| 公開日 |
2012-6-4
|
| DOI |
10.1084/jem.20112741
|
| PII |
jem.20112741
|
| PMID |
22641383
|
| PMC |
PMC3371732
|
| MeSH |
Amino Acid Motifs
Amino Acid Sequence
Animals
B7-H1 Antigen / metabolism
CD8-Positive T-Lymphocytes / metabolism
Lymphocyte Activation
Mice
Mice, Mutant Strains
Molecular Sequence Data
Phosphorylation
Programmed Cell Death 1 Receptor / genetics
Programmed Cell Death 1 Receptor / immunology
Programmed Cell Death 1 Receptor / metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
Receptors, Antigen, T-Cell / metabolism*
Signal Transduction
T-Lymphocytes / metabolism
Tyrosine / metabolism
|
| IF |
11.743
|
| 引用数 |
376
|
|
WOS 分野
|
IMMUNOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| 実験動物マウス |
RBRC02142 |
