論文 - 詳細
| RRC ID | 88485 |
|---|---|
| 著者 | Takehara T, Wakamatsu E, Machiyama H, Nishi W, Emoto K, Azuma M, Soejima K, Fukunaga K, Yokosuka T. |
| タイトル | PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment. |
| ジャーナル | Commun Biol |
| Abstract |
The coinhibitory receptor, PD-1, is of major importance for the suppression of T cell activation in various types of immune responses. A high-resolution imaging study showed that PD-1 forms a coinhibitory signalosome, "PD-1 microcluster", with the phosphatase, SHP2, to dephosphorylate the TCR/CD3 complex and its downstream signaling molecules. Such a consecutive reaction entirely depended on PD-1-PD-L1/2 binding. PD-L2 is expressed on professional antigen-presenting cells and also on some tumor cells, which possibly explains the discrepant efficacy of immune checkpoint therapy for PD-L1-negative tumors. Here, we performed precise imaging analysis of PD-L2 forming PD-1-PD-L2 clusters associating with SHP2. PD-L2 could compete with PD-L1 for binding to PD-1, occupying the same space at TCR microclusters. The PD-1 microcluster formation was inhibited by certain mAbs with functional consequences. Thus, PD-1 microcluster formation provides a visible index for the effectiveness of anti-PD-1- or anti-PD-L1/2-mediated T cell suppression. PD-L2 may exert immune suppressive responses cooperatively with PD-L1 on the microcluster scale. |
| 巻・号 | 4(1) |
| ページ | 581 |
| 公開日 | 2021-5-14 |
| DOI | 10.1038/s42003-021-02111-3 |
| PII | 10.1038/s42003-021-02111-3 |
| PMID | 33990697 |
| PMC | PMC8121797 |
| MeSH | Animals CD8-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / metabolism Cells, Cultured Dendritic Cells / immunology* Dendritic Cells / metabolism Lymphocyte Activation / immunology* Mice Mice, Inbred C57BL Mice, Knockout Programmed Cell Death 1 Ligand 2 Protein / genetics Programmed Cell Death 1 Ligand 2 Protein / metabolism* Programmed Cell Death 1 Receptor / physiology* Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism* Signal Transduction |
| IF | 4.165 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02142 |