| First Author | Demetriou P | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 10 | Pages | 1232-1243 |
| PubMed ID | 32929275 | Mgi Jnum | J:305840 |
| Mgi Id | MGI:6706592 | Doi | 10.1038/s41590-020-0770-x |
| Citation | Demetriou P, et al. (2020) A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals. Nat Immunol 21(10):1232-1243 |
| abstractText | The CD2-CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse, with cellular or artificial APC, in a pattern we refer to as a 'CD2 corolla'. The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators. The corolla amplified active phosphorylated Src-family kinases (pSFK), LAT and PLC-gamma over T cell receptor (TCR) alone. CD2-CD58 interactions in the corolla boosted signaling by 77% as compared with central CD2-CD58 interactions. Engaged PD-1 invaded the CD2 corolla and buffered CD2-mediated amplification of TCR signaling. CD2 numbers and motifs in its cytoplasmic tail controlled corolla formation. CD8(+) tumor-infiltrating lymphocytes displayed low expression of CD2 in the majority of people with colorectal, endometrial or ovarian cancer. CD2 downregulation may attenuate antitumor T cell responses, with implications for checkpoint immunotherapies. |
