Naper Christian, Hayashi Shigenari, Joly Etienne, Butcher Geoffrey W, Rolstad Bent, Vaage John T, Ryan James C
Department of Anatomy, University of Oslo, Oslo, Norway.
Eur J Immunol. 2002 Jul;32(7):2031-6. doi: 10.1002/1521-4141(200207)32:7<2031::AID-IMMU2031>3.0.CO;2-H.
We have exploited strain-specific differences in the NK allorecognition repertoires to generate rat monoclonal antibodies against receptors involved in the control of allogeneic responses by rat NK cells. The monoclonal antibody STOK2 binds to a homodimeric glycoprotein that has been implicated as an inhibitory receptor for an MHC molecule in the PVG strain. In the present study, we haveidentified this glycoprotein as a novel rat Ly49 receptor (Ly49i2) containing an immunoreceptor tyrosine-based inhibitory motif. Ligation of the Ly49i2 receptor induces inhibitory signals, and Ly49i2 coprecipitates with the inhibitory tyrosine phosphatase SHP-1 in stably transfected RNK-16 cells. Moreover, it inhibits natural killing of lymphoblast targets and transfected fibroblast targets expressingthe classical MHC class Ia allele RT1-A1(c). Ly49i2, therefore, is an inhibitory receptor for specific MHC class Ia molecules, similar to inhibitory members of the mouse Ly49 family.
我们利用自然杀伤细胞(NK)同种异体识别库中的品系特异性差异,制备了针对参与大鼠NK细胞控制同种异体反应的受体的大鼠单克隆抗体。单克隆抗体STOK2与一种同型二聚体糖蛋白结合,该糖蛋白被认为是PVG品系中MHC分子的抑制性受体。在本研究中,我们已将这种糖蛋白鉴定为一种新型大鼠Ly49受体(Ly49i2),其含有基于免疫受体酪氨酸的抑制基序。Ly49i2受体的连接可诱导抑制性信号,并且在稳定转染的RNK-16细胞中,Ly49i2与抑制性酪氨酸磷酸酶SHP-1共沉淀。此外,它可抑制表达经典MHC I类等位基因RT1-A1(c)的淋巴母细胞靶标和转染成纤维细胞靶标的自然杀伤作用。因此,Ly49i2是特异性MHC I类分子的抑制性受体,类似于小鼠Ly49家族的抑制性成员。