Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)
Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)
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DOI：
10.1093/intimm/dxh059
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Shibuya, A
中科院分区：
文献类型：
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作者：
Tahara-Hanaoka, S;Shibuya, K;Shibuya, A
CD226 (DNAM-1) 是一种粘附分子，参与 NK 和 T 细胞介导的针对某些肿瘤的细胞毒性。在这里，我们确定了人类脊髓灰质炎病毒受体相关 (PRR) 家族成员 CD155 [脊髓灰质炎病毒受体 (PVR)] 和 CD112 (nectin-2/PRR-2) 作为人类 CD226 的配体。人 CD155 和/或 CD112 的异位表达使小鼠 BW5147 T 细胞更容易受到 IL-2 激活的 T 和 NK 细胞介导的细胞毒性的影响，并且抗 CD226 mAb 特异性抑制杀伤作用，这证明了 CD226 与 CD155 和 CD112 的功能相互作用。尽管可溶性 CD226 与 CD155 或 CD112 之间的结合亲和力相当，但细胞表面 CD112 的同质相互作用可能会对 CD226 与 CD112 的结合产生不利影响。我们还证明 CD226 和 LFA-1 与其各自配体的连接协同触发 T 和 NK 细胞的细胞毒性和细胞因子分泌。
CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226. Ectopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more susceptible to IL-2-activated T and NK cell-mediated cytotoxicity, and killing was specifically inhibited by anti-CD226 mAb, demonstrating functional interactions of CD226 with CD155 and CD112. Although the binding affinities between soluble CD226 and CD155 or CD112 were comparable, the homophilic interaction of cell-surface CD112 may adversely affect CD226 binding to CD112. We also demonstrate that ligation of CD226 and LFA-1 with their respective ligands cooperates in triggering cytotoxicity and cytokine secretion by T and NK cells.