A dynamic CD2 rich compartment at the outer edge of the immunological synapse boosts and integrates signals

Journal article

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-γ 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.

Authors: Demetriou, P; Abu-Shah, E; Valvo, S; McCuaig, S; Mayya, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Immunology
• Volume: 21
• Pages: 1232-1243
• Publication date: 2020-09-14
• Acceptance date: 2020-07-28
• DOI: 10.1038/s41590-020-0770-x
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English
• Keywords: FFR