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A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
Nature Immunology ( IF 27.7 ) Pub Date : 2020-09-14 , DOI: 10.1038/s41590-020-0770-x
Philippos Demetriou 1 , Enas Abu-Shah 1, 2 , Salvatore Valvo 1 , Sarah McCuaig 1 , Viveka Mayya 1, 3 , Audun Kvalvaag 1 , Thomas Starkey 4 , Kseniya Korobchevskaya 1 , Lennard Y W Lee 4 , Matthias Friedrich 1 , Elizabeth Mann 1 , Mikhail A Kutuzov 2 , Matteo Morotti 5 , Nina Wietek 5 , Heather Rada 1 , Shamsideen Yusuf 1 , Jehan Afrose 1, 3, 6 , Anastasios Siokis 7 , , Michael Meyer-Hermann 7, 8 , Ahmed Ashour Ahmed 5 , David Depoil 1, 3, 9 , Michael L Dustin 1, 3
Affiliation  

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.



中文翻译:


免疫突触外缘的动态富含 CD2 的区室可增强并整合信号。



CD2-CD58 识别系统促进粘附和信号传导,并对抗人类 T 细胞的耗竭。我们发现 CD2 定位于成熟免疫突触的外缘,与细胞或人工 APC 一起,以我们称为“CD2 花冠”的模式。花冠捕获了 CD28、ICOS、CD226 和 SLAM-F1 共刺激器。与单独的 T 细胞受体 (TCR) 相比,花冠放大了活性磷酸化 Src 家族激酶 (pSFK)、LAT 和 PLC-γ。与中央 CD2-CD58 相互作用相比,花冠中的 CD2-CD58 相互作用将信号传导增强了 77%。参与的 PD-1 侵入 CD2 花冠并缓冲 CD2 介导的 TCR 信号放大。细胞质尾部的 CD2 数量和基序控制花冠的形成。在大多数结直肠癌、子宫内膜癌或卵巢癌患者中,CD8 +肿瘤浸润淋巴细胞显示 CD2 低表达。 CD2 下调可能会减弱抗肿瘤 T 细胞反应,从而影响检查点免疫疗法。

更新日期:2020-09-14
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