Essential role of CD155 glycosylation in functional binding to DNAM-1 on natural killer cells.

IF 4.8 4区 医学 Q2 IMMUNOLOGY International immunology Pub Date : 2024-04-27 DOI:10.1093/intimm/dxae005
Saeko Tahara, Genki Okumura, Tomohei Matsuo, Akira Shibuya, Kazuko Shibuya
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Abstract

The cluster of differentiation 155 (CD155) is highly expressed on tumor cells and augments or inhibits the cytotoxic activities of natural killer (NK) cells and T cells through its receptor ligands DNAX accessory molecule 1 (DNAM-1) and T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), respectively. Although CD155 is heavily glycosylated, the role of glycosylation of CD155 in the cytotoxic activity of effector lymphocytes remains unknown. Here, we show that the N-linked glycosylation at residue 105 (N105 glycosylation) in the first Ig-like domain of CD155 is involved in the binding of CD155 to both DNAM-1 and TIGIT. The N105 glycosylation also plays an essential role to induce signaling in both DNAM-1 and TIGIT reporter cells. Moreover, we show that the N105 glycosylation of CD155 contributes preferentially to the DNAM-1-mediated activating signal over the TIGIT-mediated inhibitory signal in NK cells. Our results demonstrated the important role of the N105 glycosylation of CD155 in DNAM-1 and TIGIT functions and shed new light on the understanding of tumor immune responses.

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CD155 糖基化在与自然杀伤细胞上的 DNAM-1 功能性结合中的重要作用。
CD155在肿瘤细胞上高度表达,并分别通过其受体配体DNAM-1和T细胞免疫球蛋白免疫受体酪氨酸抑制基团结构域(TIGIT)增强或抑制自然杀伤(NK)细胞和T细胞的细胞毒活性。虽然 CD155 被大量糖基化,但 CD155 的糖基化在效应淋巴细胞的细胞毒性活性中的作用仍然未知。在这里,我们发现 CD155 的第一个免疫球蛋白样结构域中残基 105 处的 N-连接糖基化(N105 糖基化)参与了 CD155 与 DNAM-1 和 TIGIT 的结合。N105 糖基化在 DNAM-1 和 TIGIT 报告细胞中诱导信号传导中也起着至关重要的作用。此外,我们还发现在 NK 细胞中,CD155 的 N105 糖基化对 DNAM-1 介导的激活信号的作用优于 TIGIT 介导的抑制信号。我们的研究结果证明了 CD155 的 N105 糖基化在 DNAM-1 和 TIGIT 功能中的重要作用,并为理解肿瘤免疫反应提供了新的思路。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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