Nakamura Yuho, Naito Keisuke, Yamashita-Kanemaru Yumi, Komori Daisuke, Hirochika Rei, Shibuya Akira, Shibuya Kazuko
1 Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan .
2 Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba , Tsukuba, Japan .
Monoclon Antib Immunodiagn Immunother. 2018 Apr;37(2):105-109. doi: 10.1089/mab.2018.0001. Epub 2018 Apr 12.
T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear. Although analyses of mouse tumor model using a neutralizing anti-mouse TIGIT (mTIGIT) mAbs should be useful to address this issue, there are limitations to this type of studies due to unavailability of neutralizing anti-mTIGIT mAbs. In this study, we generated five clones of anti-mTIGIT mAbs, designated TX99, TX100, TX103, TX104, and TX105. We show that TX99 and TX100 showed the strongest binding to TIGIT. We also show that TX99 interfered with the interaction between TIGIT and CD155 and increased NK cell-mediated cytotoxicity against CD155-expressing RMA-S cells. Thus, TX99 is a unique neutralizing mAb that can be used for studies of mTIGIT functions.
T细胞免疫球蛋白和ITIM结构域（TIGIT）是一种抑制性免疫受体，表达于自然杀伤细胞、效应性和记忆性T细胞以及调节性T细胞（Tregs）上。TIGIT的配体是CD155（PVR）和CD112（PVRL2，nectin-2），它们广泛表达于造血细胞和非造血细胞上。TIGIT负向调节抗肿瘤反应，但促进自身免疫反应。尽管中和性抗人TIGIT单克隆抗体正在进行癌症临床试验，但TIGIT与配体相互作用的阻断如何显示肿瘤免疫仍不清楚。尽管使用中和性抗小鼠TIGIT（mTIGIT）单克隆抗体分析小鼠肿瘤模型对解决这个问题应该有用，但由于缺乏中和性抗mTIGIT单克隆抗体，这类研究存在局限性。在本研究中，我们产生了五个抗mTIGIT单克隆抗体克隆，命名为TX99、TX100、TX103、TX104和TX105。我们发现TX99和TX100与TIGIT的结合最强。我们还发现TX99干扰了TIGIT与CD155之间的相互作用，并增强了自然杀伤细胞对表达CD155的RMA-S细胞的细胞毒性。因此，TX99是一种独特的中和性单克隆抗体，可用于研究mTIGIT的功能。
