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A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
Demetriou, Philippos Abu-Shah, Enas Valvo, Salvatore McCuaig, Sarah Mayya, Viveka Kvalvaag, Audun Starkey, Thomas Korobchevskaya, Kseniya Lee, Lennard Y W Friedrich, Matthias
Demetriou, Philippos
Abu-Shah, Enas
Valvo, Salvatore
McCuaig, Sarah
Mayya, Viveka
Kvalvaag, Audun
Starkey, Thomas
Korobchevskaya, Kseniya
Lee, Lennard Y W
Friedrich, Matthias
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2020-09-14
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s41590-020-0770-x(1).pdf
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Abstract
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.
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en
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1529-2916
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Attribution-ShareAlike 4.0 International