Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody
Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody
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新型抗 DNAM-1 单克隆抗体的建立和表征
DOI：
10.1089/mab.2012.0083
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发表时间：
2013
影响因子：
--
通讯作者：
Shibuya K.
中科院分区：
文献类型：
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作者：
Yamashita Y;Abe F;Hirochika R;Tahara-Hanaoka S;Shibuya A;Shibuya K.
DNAM-1（CD 226）在大多数NK细胞、CD 8 +T细胞和CD 4 +T细胞上表达，并在与靶细胞或抗原呈递细胞上表达的配体CD 155或CD 112结合后介导这些细胞中的活化信号。DNAM-1在NK细胞和CD 8 +T细胞介导的肿瘤免疫以及小鼠移植物抗宿主病（GVHD）的发生中起重要作用。本实验室制备了抗小鼠DNAM-1的单克隆抗体TX 42，它能抑制DNAM-1与其配体CD 155和CD 112的结合，并能抑制NK细胞和CD 8 +T细胞的活化。注射TX 42可减轻小鼠GVHD的发生。在这里，我们产生了一个新的抗DNAM-1单克隆抗体，TX 92。TX 92类似地染色原代脾细胞，包括CD 8+和CD 4 +T细胞和NK细胞。TX 92和TX 42干扰DNAM-1与配体CD 155和CD 112之间的相互作用。然而，TX 92识别不同的表位，并且与TX 42不同，TX 92在体内部分但不完全耗尽外周血（PB）CD 8 +T细胞。因此，TX 92是一种独特的MAb，其特征不仅在于DNAM-1与配体结合的抑制功能，而且还在于PB CD 8 +T细胞的部分耗竭功能。
DNAM-1 (CD226) is expressed on the majority of NK cells, CD8+T cells, and CD4+T cells and mediates an activating signal in these cells upon binding to the ligands CD155 or CD112 expressed on target cells or antigen-presenting cells. DNAM-1 plays an important role in tumor immunity mediated by NK cells and CD8+T cells and the development of graft-versus-host disease (GVHD) in mice. We previously generated a monoclonal antibody against mouse DNAM-1, TX42, which inhibited DNAM-1 binding to its ligands CD155 and CD112 and inhibited activation of NK cells and CD8+T cellsin vitro. Injection of mice with TX42 ameliorated the development of GVHD in mice. Here, we generated a new clone of anti-DNAM-1 MAb, TX92. TX92 similarly stained primary spleen cells, including CD8+and CD4+T cells and NK cells. TX92 as well as TX42 interfered with the interaction between DNAM-1 and ligands CD155 and CD112. However, TX92 recognizes a different epitope and, unlike TX42 partially, but not completely, depleted peripheral blood (PB) CD8+T cellsin vivo. Thus, TX92 is a unique MAb that is characterized not only by inhibitory function of DNAM-1 binding to the ligands but also by function of partial depletion of PB CD8+T cells.