al-Shamkhani A, Birkeland M L, Puklavec M, Brown M H, James W, Barclay A N
MRC Cellular Immunology Unit, University of Oxford, GB.
Eur J Immunol. 1996 Aug;26(8):1695-9. doi: 10.1002/eji.1830260805.
OX40, a member of the tumor necrosis factor (TNF) receptor/nerve growth factor (NGF) receptor superfamily was first identified as a marker of activated rat CD4+ cells with the MRC OX40 monoclonal antibody (mAb). A ligand for OX40 (called OX40 ligand or OX40L) has recently been identified and has sequence similarity to TNF. Mouse OX40L-immunoglobulin fusion protein (OX40L-Ig) binds to activated mouse CD4+ and CD8+ cells (Baum, P. R. et al., EMBO J. 1994. 13: 3992) suggesting that OX40 could have a differential pattern of expression on mouse and rat T cells. This, however, did not rule out the presence of an alternative receptor on CD8+ cells that also binds the OX40L. We have compared the binding of the MRC OX40 mAb with that of OX40L-Ig to activated rat lymph node cells and show that both recognize the same protein, namely OX40 which is expressed on CD4+ and CD4+ CD8 alpha+ cells, but not on CD4-CD8+ cells. We have raised a new mAb (MRC OX86) using recombinant mouse OX40 protein and show by two-color flow cytometry that mouse OX40 is expressed on CD4 and CD8 single-positive cells. In addition, the new MRC OX86 mAb, unlike the MRC OX40 mAb, did not block binding of the OX40L. We conclude that OX40 is differentially expressed on activated mouse and rat T cells and is the sole receptor for the OX40L.
OX40是肿瘤坏死因子(TNF)受体/神经生长因子(NGF)受体超家族的成员,最初是用MRC OX40单克隆抗体(mAb)作为活化大鼠CD4+细胞的标志物被鉴定出来的。最近已经鉴定出OX40的一种配体(称为OX40配体或OX40L),其与TNF具有序列相似性。小鼠OX40L-免疫球蛋白融合蛋白(OX40L-Ig)能与活化的小鼠CD4+和CD8+细胞结合(鲍姆,P.R.等人,《欧洲分子生物学组织杂志》,1994年。13:3992),这表明OX40在小鼠和大鼠T细胞上可能具有不同的表达模式。然而,这并未排除CD8+细胞上存在也能结合OX40L的替代受体的可能性。我们比较了MRC OX40 mAb与OX40L-Ig对活化大鼠淋巴结细胞的结合情况,结果表明两者识别的是同一种蛋白,即表达于CD4+和CD4+ CD8α+细胞而非CD4-CD8+细胞上的OX40。我们用重组小鼠OX40蛋白制备了一种新的mAb(MRC OX86),通过双色流式细胞术显示小鼠OX40表达于CD4和CD8单阳性细胞上。此外,与MRC OX40 mAb不同,新的MRC OX86 mAb不会阻断OX40L的结合。我们得出结论,OX40在活化的小鼠和大鼠T细胞上存在差异表达,并且是OX40L的唯一受体。