| RRC ID |
88485
|
| Author |
Takehara T, Wakamatsu E, Machiyama H, Nishi W, Emoto K, Azuma M, Soejima K, Fukunaga K, Yokosuka T.
|
| Title |
PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment.
|
| Journal |
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.
|
| Volume |
4(1)
|
| Pages |
581
|
| Published |
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
|
| Resource |
| Mice |
RBRC02142 |
