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两种单克隆抗CD3抗体可在人T淋巴细胞激活过程中诱导不同事件。

Two monoclonal anti-CD3 antibodies can induce different events in human T lymphocyte activation.

作者信息

Roosnek E E, Van Lier R A, Aarden L A

机构信息

Basel Institute for Immunology, Switzerland.

出版信息

Eur J Immunol. 1987 Oct;17(10):1507-10. doi: 10.1002/eji.1830171019.

DOI:10.1002/eji.1830171019
PMID:3500058
Abstract

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.

摘要

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。

相似文献

1
Two monoclonal anti-CD3 antibodies can induce different events in human T lymphocyte activation.两种单克隆抗CD3抗体可在人T淋巴细胞激活过程中诱导不同事件。
Eur J Immunol. 1987 Oct;17(10):1507-10. doi: 10.1002/eji.1830171019.
2
Functional studies with anti-CD3 heavy chain isotype switch-variant monoclonal antibodies. Accessory cell-independent induction of interleukin 2 responsiveness in T cells by epsilon-anti-CD3.抗CD3重链同种型转换变体单克隆抗体的功能研究。ε-抗CD3对T细胞中白细胞介素2反应性的辅助细胞非依赖性诱导。
J Immunol. 1987 Nov 1;139(9):2873-9.
3
Mechanisms by which accessory cells contribute in growth of resting T lymphocytes initiated by OKT3 antibody.辅助细胞促进OKT3抗体引发的静止T淋巴细胞生长的机制。
Eur J Immunol. 1985 Jul;15(7):645-51. doi: 10.1002/eji.1830150702.
4
Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation.固定化抗CD3单克隆抗体刺激能力的差异:对白细胞介素-1作为T细胞激活辅助信号的可变依赖性。
Immunology. 1991 Feb;72(2):269-76.
5
Immobilized anti-CD3 monoclonal antibodies induce accessory cell-independent lymphokine production, proliferation and helper activity in human T lymphocytes.固定化抗CD3单克隆抗体可诱导人T淋巴细胞产生不依赖辅助细胞的淋巴因子、增殖并具有辅助活性。
Immunology. 1989 Sep;68(1):45-50.
6
Role of interleukin 2 receptor beta chain in initiating anti-CD3 and interleukin 2-induced proliferation of human resting T cells.白细胞介素2受体β链在启动抗CD3和白细胞介素2诱导的人静止T细胞增殖中的作用。
Eur J Immunol. 1990 Sep;20(9):1981-7. doi: 10.1002/eji.1830200916.
7
T cell activation by cross-linking anti-CD3 antibodies with second anti-T cell antibodies: dual antibody cross-linking mimics physical monocyte interaction.通过将抗CD3抗体与第二种抗T细胞抗体交联来激活T细胞:双抗体交联模拟了物理单核细胞相互作用。
Eur J Immunol. 1987 Nov;17(11):1611-8. doi: 10.1002/eji.1830171114.
8
Human T cell activation: differential response to anti-CD28 as compared to anti-CD3 monoclonal antibodies.人类T细胞活化:与抗CD3单克隆抗体相比,对抗CD28的不同反应。
Eur J Immunol. 1989 May;19(5):881-7. doi: 10.1002/eji.1830190515.
9
Induction of T cell proliferation with anti-CD3 switch-variant monoclonal antibodies: effects of heavy chain isotype in monocyte-dependent systems.抗CD3开关变体单克隆抗体诱导T细胞增殖:重链同种型在单核细胞依赖系统中的作用
Eur J Immunol. 1987 Nov;17(11):1599-604. doi: 10.1002/eji.1830171112.
10
The required interaction between monocytes and peripheral blood T lymphocytes (T-PBL) upon activation via CD2 or CD3. Role of HLA class I molecules from accessory cells and the differential response of T-PBL subsets.单核细胞与外周血T淋巴细胞(T-PBL)经CD2或CD3激活后所需的相互作用。辅助细胞HLA I类分子的作用以及T-PBL亚群的差异反应。
Eur J Immunol. 1988 Aug;18(8):1187-94. doi: 10.1002/eji.1830180807.

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2
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Triggering T cells by otherwise inert hybrid anti-CD3/antitumor antibodies requires encounter with the specific target cell.通过原本无活性的抗CD3/抗肿瘤杂交抗体触发T细胞需要与特定靶细胞相遇。
J Exp Med. 1989 Jul 1;170(1):297-302. doi: 10.1084/jem.170.1.297.