Homophilic interaction of NTBA, a member of the CD2 molecular family:: induction of cytotoxicity and cytokine release in human NK cells
Homophilic interaction of NTBA, a member of the CD2 molecular family:: induction of cytotoxicity and cytokine release in human NK cells
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DOI：
10.1002/eji.200424886
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Bottino, C
中科院分区：
文献类型：
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作者：
Falco, M;Marcenaro, E;Bottino, C
NK-T-B抗原（NTBA）是在人NK细胞活化中作为辅助受体起作用的CD2家族成员。几种受体/配体相互作用发生在该分子家族的不同成员之间。在这项研究中，为了鉴定NTBA的天然配体，我们产生了由NTBA胞外区与人IgG 1的Fc部分融合形成的嵌合蛋白（称为NTBA-Fc *）。NTBA-Fc * 特异性结合NTBA细胞转染子，但不结合用其它CD2家族成员（包括CD2、CD48、CD84、CD150、CD229和CD244）转染的细胞。此外，NTBA-Fc * 还结合NTBA（+）但不结合NTBA（-）T细胞系。酶联免疫吸附测定、等离子体共振分析以及NTBA-Fc * 介导的NTBA表面表达下调进一步证实了NTBA/NTBA嗜同性相互作用的发生。在功能上，在NK细胞中，NTBA-Fc * 促进IFN-γ和TNF-α的强烈产生。此外，与未转染的细胞相比，NTBA转染的靶细胞显示出对NK介导的杀伤的敏感性增加，并且这种作用被抗NTBA mAb特异性抑制。总而言之，我们的数据表明NTBA的特征是自我识别。
NK-T-B antigen (NTBA) is a CD2 family member that functions as a coreceptor in human NK cell activation. Several receptor/ligand interactions occur between different members of this molecular family. In this study, in order to identify the natural ligand of NTBA, we produced a chimeric protein formed by the NTBA extracellular region fused with the Fc portion of human IgG1 (termed NTBA-Fc*). NTBA-Fc* specifically binds to NTBA cell transfectants but not to cells transfected with other CD2 family members including CD2, CD48, CD84, CD1 50, CD229, and CD244. Moreover, NTBA-Fc* also binds to NTBA(+) but not to NTBA(-) T cell lines. Enzyme-linked immunosorbent assays, plasmon resonance analysis, as well as NTBA-Fc*-mediated down-regulation of NTBA surface expression further confirmed the occurrence of NTBA/NTBA homophilic interaction. Functionally, in NK cells, NTBA-Fc* promoted a strong production of IFN-gamma and TNF-alpha. Moreover, NTBA-transfected targets displayed increased susceptibility to NK-mediated killing as compared to untransfected cells and this effect was specifically inhibited by anti-NTBA mAb. Altogether our data indicate that NTBA is characterized by self recognition.