Monoclonal antibody 2D10 recognizes a novel T cell costimulatory molecule on activated murine B lymphocytes.
Monoclonal antibody 2D10 recognizes a novel T cell costimulatory molecule on activated murine B lymphocytes.
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单克隆抗体 2D10 可识别激活的鼠 B 淋巴细胞上的新型 T 细胞共刺激分子。
DOI：
10.4049/jimmunol.152.5.2105
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发表时间：
1994
影响因子：
4.4
通讯作者：
N. Nabavi
中科院分区：
文献类型：
--
作者：
C. Chen;D. Faherty;A. Gault;S. Connaughton;G. Powers;D. Godfrey;N. Nabavi
我们已经开发了一组针对二丁基camp活化的5C2细胞的大鼠单抗。在这个小组中，一个mAb， 1G10，识别小鼠B7。另一种名为2D10的单抗不与小鼠B7结合，但可以识别仅在二丁基camp激活的5C2小鼠B淋巴瘤细胞或lps刺激的脾B细胞上表达的表面分子。这种新分子被称为早期T细胞共刺激分子-1 （ETC-1）。从活化的5C2细胞和脾B细胞中，mAb 2D10免疫沉淀59- 60 kda的蛋白，这与从相同细胞群中沉淀的47- 55 kda的小鼠B7蛋白不同。FACS分析显示，与B7相比，ETC-1在5C2细胞上的表达是由较低浓度的二丁基cAMP诱导的，并且表现出更快的动力学。lps刺激的脾B细胞表达相对较低水平的B7和较高水平的ETC-1。重要的是，在使用活化的5C2细胞作为APC的银呈送实验中，C8A3 T杂交体分泌IL-2被单抗2D10部分抑制，而被单抗2D10和1G10以剂量依赖和协同的方式完全阻断。在单向原发性MLR中，单抗2D10在0.1至1微克/毫升的浓度下抑制T细胞增殖19%至56%。然而，当两种单抗联合添加时，观察到加性阻断效应（高达76%）。因此，我们的数据表明，激活的小鼠B细胞上存在一种新的T细胞共刺激分子，该分子与B7合作，可能在最佳T细胞激活中发挥关键作用。
We have developed a panel of rat mAbs against dibutyryl cAMP-activated 5C2 cells. In this panel, one mAb, 1G10, recognized murine B7. Another mAb designated 2D10 did not bind to murine B7 but could recognize a surface molecule expressed only on dibutyryl cAMP-activated 5C2 mouse B lymphoma cells or on LPS-stimulated splenic B cells. This new molecule is referred to as early T cell costimulatory molecule-1 (ETC-1). From both activated 5C2 cells and splenic B cells, mAb 2D10 immunoprecipitated a 59- to 60-kDa protein, which was different from the 47- to 55-kDa murine B7 protein precipitated from the same cell populations. FACS analysis showed that, in contrast to B7, the expression of ETC-1 on 5C2 cells was induced by lower concentrations of dibutyryl cAMP and displayed a faster kinetics. LPS-stimulated splenic B cells expressed relatively low levels of B7 and much higher levels of ETC-1. Importantly, in an Ag presentation assay using activated 5C2 cells as APC, the secretion of IL-2 by C8A3 T hybrids was partially inhibited by mAb 2D10 alone and completely blocked by combination use of mAbs 2D10 and 1G10 in a dose-dependent and synergistic fashion. In a one-way primary MLR, mAb 2D10 alone at 0.1 to 1 microgram/ml inhibited T cell proliferation by 19 to 56%. However, an additive blocking effect (up to 76%) was observed when two mAbs were added in combination. Thus, our data have demonstrated that a novel T cell costimulatory molecule is present on activated murine B cells, which, in cooperation with B7, may play a critical role in optimal T cell activation.