論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 105 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.5 |
| リソース情報 | |
| 実験動物マウス | RBRC02142 |