| Literature DB >> 32929275 |
Philippos Demetriou1, Enas Abu-Shah1,2, Salvatore Valvo1, Sarah McCuaig1, Viveka Mayya1,3, Audun Kvalvaag1, Thomas Starkey4, Kseniya Korobchevskaya1, Lennard Y W Lee4, Matthias Friedrich1, Elizabeth Mann1, Mikhail A Kutuzov2, Matteo Morotti5, Nina Wietek5, Heather Rada1, Shamsideen Yusuf1, Jehan Afrose1,3,6, Anastasios Siokis7, Michael Meyer-Hermann7,8, Ahmed Ashour Ahmed5, David Depoil1,3,9, Michael L Dustin10,11.
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.Entities:
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Year: 2020 PMID： 32929275 PMCID： PMC7611174 DOI： 10.1038/s41590-020-0770-x
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606