Tezuka K, Tsuji T, Hirano D, Tamatani T, Sakamaki K, Kobayashi Y, Kamada M
Pharmaceutical Frontier Research Laboratories, JT Inc., Fukuura 1-13-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Biochem Biophys Res Commun. 2000 Sep 16;276(1):335-45. doi: 10.1006/bbrc.2000.3466.
Activation-inducible lymphocyte immuno-mediatory molecule (AILIM) is an inducible cell surface glycoprotein expressed on thymocytes and activated lymphocytes. Specific monoclonal antibody to rat AILIM induced the cell aggregation of a rat thymoma cell line and ConA-activated splenocytes. In the present study, we identified the primary structure of two species of rat AILIM by expression cloning. We also cloned mouse and human AILIM homologues and the predicted amino acid sequences were identical to those of the inducible costimulator ICOS/CRP-1, which belongs to the CD28/CTLA4 family. Although the human and mouse AILIM/ICOS molecule is localized on T-cells, the major population of AILIM/ICOS-positive cells in rat splenocyte was CD45RA-positive B-cells. The expression level of AILIM/ICOS on T-cells was relatively low; however, its expression was drastically induced by the treatment with PMA plus Ca-ionophore or the engagement of CD3 and these costimulatory molecules. Almost all T-cells exhibited potency as to its expression. Functional analysis of AILIM/ICOS demonstrated that AILIM-mediated costimulation was relatively weak compared to that of human.
激活诱导淋巴细胞免疫调节分子(AILIM)是一种在胸腺细胞和活化淋巴细胞上表达的可诱导细胞表面糖蛋白。针对大鼠AILIM的特异性单克隆抗体可诱导大鼠胸腺瘤细胞系和刀豆蛋白A激活的脾细胞发生细胞聚集。在本研究中,我们通过表达克隆鉴定了两种大鼠AILIM的一级结构。我们还克隆了小鼠和人类AILIM同源物,预测的氨基酸序列与属于CD28/CTLA4家族的诱导性共刺激分子ICOS/CRP-1相同。尽管人和小鼠的AILIM/ICOS分子定位于T细胞,但大鼠脾细胞中AILIM/ICOS阳性细胞的主要群体是CD45RA阳性B细胞。AILIM/ICOS在T细胞上的表达水平相对较低;然而,用佛波酯加钙离子载体处理或CD3及这些共刺激分子的结合可显著诱导其表达。几乎所有T细胞都具有表达该分子的能力。AILIM/ICOS的功能分析表明,与人类相比,AILIM介导的共刺激作用相对较弱。