A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
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DOI：
10.1038/s41590-020-0770-x
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发表时间：
2020-10
影响因子：
30.5
通讯作者：
Dustin ML
中科院分区：
文献类型：
--
作者：
Demetriou P;Abu-Shah E;Valvo S;McCuaig S;Mayya V;Kvalvaag A;Starkey T;Korobchevskaya K;Lee LYW;Friedrich M;Mann E;Kutuzov MA;Morotti M;Wietek N;Rada H;Yusuf S;Afrose J;Siokis A;Oxford IBD Cohort Investigators;Meyer-Hermann M;Ahmed AA;Depoil D;Dustin ML
CD 2-CD 58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，CD 2定位于成熟的免疫突触（IS）的外缘，与细胞或人工APC，在一个模式，我们称之为“CD 2花冠”。花冠捕获接合的CD 28、ICOS、CD 226和SLAM-F1共刺激因子。在单独的T细胞受体（TCR）上，花冠扩增活性磷酸化Src家族激酶（pSFK）、LAT和PLC-γ。与中央CD 2-CD 58相互作用相比，花冠中的CD 2-CD 58相互作用增强了77%的信号传导。CDPD-1侵入CD 2花冠并缓冲CD 2介导的TCR信号传导的扩增。细胞质尾区的CD 2数目和基序控制着花冠的形成。大多数结直肠癌、子宫内膜癌和卵巢癌患者的CD 8+肿瘤浸润淋巴细胞显示CD 2低表达。CD 2下调可能减弱抗肿瘤T细胞应答，这对检查点免疫疗法有影响。
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 (IS), 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 costimulators. 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% compared to 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 colorectal, endometrial and ovarian cancer patients. CD2 down-regulation may attenuate anti-tumor T cell responses with implications for checkpoint immunotherapies.
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