Immune regulation by new NK receptor family molecules

新NK受体家族分子的免疫调节

• 批准号: 16390141
• 负责人: ARASE Hisashi
• 金额: $ 9.54万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390141/
• 关键词: Paired receptor; PILR; CD200; Immune evasion; NK cell receptor; tumor immunology; Melanoma; NK cells; cDNAライブラリー; リガンド; 活性化レセプター; 抑制化レセプター

NK cell receptors consist of activating and inhibitory receptors. These receptors seem to have been evolved with pathogens such as viruses and seem to play an important role in host defense. In the present study, we have tried to elucidate the mechanism of immune regulation by NK cells through identification of new activating NK receptors and its ligands. We have identified activating PILR and CD200 receptors as DAP12 associating receptors from cDNA library of NK cells (Shiratori et al. J.Immunol. 2005). Furthermore, we have cloned the ligand for PILR and showed that PILR ligand play an important role for the target cell recognition by NK cells (Shiratori et al. J.Exp.Med. 2004). In addition, we have found that B16 melanoma is recognized by PILR although B16 does not express PILR-ligand. Therefore, we generated cDNA library from B16 melanoma and did expression cloning. We have cloned PILR-L2 as a ligand for PILR. Indeed, PILR-L2 expressing cells were recognized by PILR expressing cells. From these observations, PILR was found to play an important role in the target cell recognition by NK cells. Furthermore, we have found that glycosylation is involved in the ligand recognition by PILR. When certain glycosyltransferase was transfected to B16, PILR ligand exressed on B16 was not recognized by PILR anymore. PILR ligand expressed on B16 transfectants was not recognized by inhibitory PILR expressed on macrophage and B16 transfectants activated macrophage very well. Therefore, certain tumor cells seemed to have acquired the ligand for inhibitory PILR by modification of the structure of glycosylation of PILR ligand and seemed to suppress the response to tumor cells. These findings may provide a novel mechanism of immune evasion by tumor.

NK细胞受体包括激活和抑制受体。这些受体似乎是通过病毒等病原体演变而来的，并且似乎在宿主防御中起着重要作用。在本研究中，我们试图通过鉴定新活化的NK受体及其配体来阐明NK细胞免疫调节的机理。我们已经将激活的PILR和CD200受体确定为NK细胞cDNA库的DAP12受体（Shiratori等人J.Immunol。2005）。此外，我们已经将配体用于PILR，并表明PILR配体对于NK细胞的靶细胞识别起着重要作用（Shiratori等人J.Exp.Med。2004）。此外，我们发现B16黑色素瘤被PILR识别，尽管B16并未表达PILR-配体。因此，我们从B16黑色素瘤产生了cDNA文库，并进行了表达克隆。我们将PILR-L2克隆为PILR的配体。实际上，PILR-L2表达细胞通过PILR表达细胞识别。从这些观察结果中，发现PILR在NK细胞的靶细胞识别中起着重要作用。此外，我们发现糖基化参与PILR的配体识别。当将某些糖基转移酶转染至B16时，PILR不再识别B16上的PILR配体。在巨噬细胞上表达的抑制性PILR未识别出在B16转染剂上表达的PILR配体，而B16转染物很好地激活了巨噬细胞。因此，某些肿瘤细胞似乎通过修饰PILR配体的糖基化结构而获得了抑制性PILR的配体，并似乎抑制了对肿瘤细胞的反应。这些发现可能提供了通过肿瘤免疫逃避的新机制。

项目成果

Heterotypic interaction of CRTAM with Necl2 induced cell adhesion on activated NK cells and CD8^+ T cells.

CRTAM与Necl2的异型相互作用诱导细胞粘附在活化的NK细胞和CD8+T细胞上。

• 发表时间: 2005
• 期刊: International Immunology 17・9
• 作者: Arase;N.;Shiratori Ikuo;Arase Noriko
• 通讯作者: Arase Noriko

PILRαと結合するポリペプチド、およびそれをコードするポリヌクレオチド、並びにその利用

与PILRα结合的多肽、编码其的多核苷酸及其用途

• 发表时间: 2006

Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors

抑制性 NKR-P1 自然杀伤细胞受体对 Ocil/Clr-b 的自我识别缺失

• 发表时间: 2004
• 期刊: Proc.Natl.Acad.Sci.USA. 101
• 作者: Carlyle;J.R.
• 通讯作者: J.R.

NFAM1, a new ITAM^+ cell surface molecule that regulates development and signaling of B lymphocytes.

NFAM1 是一种新的 ITAM^ 细胞表面分子，可调节 B 淋巴细胞的发育和信号传导。

• 发表时间: 2004
• 期刊: Proc.Natl.Acad.Sci.USA. 101
• 作者: Ohtsuka;M.
• 通讯作者: M.

FcεRIγ-ITAM is differentially required for mast cell function in vivo.

FcεRIγ-ITAM 对体内肥大细胞功能的需求存在差异。

• 发表时间: 2004
• 期刊: J Immunol 172巻4号
• 作者: Sakurai D;Yamasaki S;Arase K;Park SY;Arase H;Konno A;Saito T.
• 通讯作者: Saito T.