Roosnek E E, Van Lier R A, Aarden L A
Basel Institute for Immunology, Switzerland.
Eur J Immunol. 1987 Oct;17(10):1507-10. doi: 10.1002/eji.1830171019.
Two monoclonal antibodies, WT32 and CLB-T3/4.2a, directed against the CD3 complex were used to study the mechanism of activation of human peripheral T lymphocytes. WT32, a mouse monoclonal IgG2a antibody with a low avidity (much less than OKT3) for the CD3 complex, effectively induces mitogenesis of purified T lymphocytes when used in the 1 ng-10 micrograms range in the presence of monocytes or recombinant interleukin 2 (IL2). In contrast, CLB-T3/4.2a, a mouse monoclonal antibody of the same isotype with a high avidity (much greater than OKT3) for the CD3 complex, induces IL2 receptor expression and IL2 responsiveness only at very low concentrations (less than 5 ng/ml), yet in the presence of monocytes this antibody induces proliferation within a similar dose range as WT32. Apparently, in the absence of accessory cells which can cross-link the antibody CD3 complexes, the binding properties (avidity) of an antibody and thereby the number of receptors that are occupied are important parameters for induction of IL2 responsiveness. Furthermore, we show that Ca2+ mobilization only occurs when the cells are stimulated by saturating amounts of antibody, so that, when the conditions are optimal for the induction of IL2 responsiveness, no Ca2+ mobilization will be detected.
使用两种针对CD3复合物的单克隆抗体WT32和CLB-T3/4.2a来研究人外周血T淋巴细胞的激活机制。WT32是一种对CD3复合物亲和力较低(远低于OKT3)的小鼠单克隆IgG2a抗体,当在单核细胞或重组白细胞介素2(IL2)存在的情况下,在1 ng - 10 μg范围内使用时,能有效诱导纯化T淋巴细胞的有丝分裂。相比之下,CLB-T3/4.2a是同一种亚型的小鼠单克隆抗体,对CD3复合物具有高亲和力(远高于OKT3),仅在非常低的浓度(低于5 ng/ml)下诱导IL2受体表达和IL2反应性,然而在单核细胞存在的情况下,该抗体在与WT32相似的剂量范围内诱导增殖。显然,在不存在能够交联抗体CD3复合物的辅助细胞时,抗体的结合特性(亲和力)以及因此被占据的受体数量是诱导IL2反应性的重要参数。此外,我们表明只有当细胞受到饱和量抗体刺激时才会发生Ca2+动员,因此,当诱导IL2反应性的条件最佳时,不会检测到Ca2+动员。