Details

Autor(en) / Beteiligte

• 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
• Meyer-Hermann, Michael
• Ahmed, Ahmed Ashour
• Depoil, David
• Dustin, Michael L

Titel

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

Ist Teil von

• Nature immunology, 2020-10, Vol.21 (10), p.1232-1243

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.