英国牛津大学Michael L. Dustin团队在研究中取得进展。他们研究发现免疫突触外缘动态CD2富含区室增强并整合信号。相关论文于2020年9月14日发表在《自然-免疫学》杂志上。

研究人员发现CD2以细胞或人工APC的方式定位于成熟免疫突触的外缘，其模式称为“ CD2花冠”。“花冠”捕获了CD28、ICOS、CD226和SLAM-F1协同刺激信号。“花冠”仅通过T细胞受体（TCR）激活活性磷酸化Src家族激酶（pSFK）、LAT和PLC-γ。与中枢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％。PD-1侵入CD2“花冠”和减弱CD2介导的TCR信号扩增。

其胞质尾部调控“花冠”形成时CD2的数目和基序。在大多数结直肠癌、子宫内膜癌或卵巢癌患者中，CD8⁺肿瘤浸润性淋巴细胞低表达CD2。CD2的下调可能会减弱抗肿瘤T细胞反应，并对免疫检查点疗法产生影响。

研究人员表示，CD2-CD58识别系统可促进人T细胞的粘附、信号传导并抵抗疲劳。

附：英文原文

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

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

Issue&Volume: 2020-09-14

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.

DOI: 10.1038/s41590-020-0770-x

Source: https://www.nature.com/articles/s41590-020-0770-x