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

Nature immunology 2020

["Demetriou, Philippos", "Abu-Shah, Enas", "Valvo, Salvatore", "McCuaig, Sarah", "Mayya, Viveka", "Kvalvaag, Audun", "Starkey, Thomas", "Korobchevskaya, Kseniya", "Lee, Lennard Y W", "Friedrich, Matthias", "Mann, Elizabeth", "Kutuzov, Mikhail A", "Morotti, Matteo", "Wietek, Nina", "Rada, Heather", "Yusuf, Shamsideen", "Afrose, Jehan", "Siokis, Anastasios", "Oxford IBD Cohort Investigators", "Meyer-Hermann, Michael", "Ahmed, Ahmed Ashour", "Depoil, David", "Dustin, Michael L"]

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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