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针对人α/β T细胞受体共同表位的单克隆抗体优先激活CD45RA + T细胞。

Monoclonal antibodies to common epitopes of the human alpha/beta T-cell receptor preferentially activate CD45RA+ T-cells.

作者信息

Schwinzer R, Schlitt H J, Wonigeit K

机构信息

Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Federal Republic of Germany.

出版信息

Cell Immunol. 1992 Mar;140(1):31-41. doi: 10.1016/0008-8749(92)90174-n.

DOI:10.1016/0008-8749(92)90174-n
PMID:1531453
Abstract

The murine monoclonal antibody BMA 031 (IgG2b) is directed to a monomorphic epitope on the human alpha/beta T-cell receptor. In contrast to anti-CD3 antibodies of the IgG2b isotype, BMA 031 is able to induce a proliferative response in T-cells from IgG2b low responders. This response occurs independently of cross-linking conditions indicating that the mode of activation differs from stimulation by the anti-CD3 antibody OKT3 (IgG2a) which strictly depends on cross-linking conditions. to further characterize the stimulatory potential of the two antibodies we studied the lymphocyte subsets responsive to stimulation by BMA 031 and OKT3. In CD45RA+ cells both antibodies exhibited similar effects. They induced weak expression of the 55-kDa chain of the interleukin-2 receptor (CD25), virtually no interleukin-2 secretion, but nevertheless strong proliferation. In CD45R0+ cells OKT3 and BMA 031 showed markedly different effects. OKT3 stimulated strong CD25 expression, strong interleukin-2 production, and marked proliferation. In contrast, CD45R0+ cells stimulated by BMA 031 showed only weak CD25 expression but neither interleukin-2 production nor proliferation. These data suggest that CD45RA+ and CD45R0+ cells differ in their capability to produce interleukin-2 upon stimulation via the CD3/T-cell receptor complex and also in the requirement for interleukin-2 to mount a proliferative response. The differential effect of OKT3 and BMA 031 in CD45R0+ cells probably results from the failure of BMA 031 to trigger interleukin-2 production which may be a consequence of its inability to induce CD3/T-cell receptor cross-linking in IgG2b low responders BMA 031 is therefore a useful tool for the selective activation of CD45RA+ cells in these individuals.

摘要

鼠单克隆抗体BMA 031(IgG2b)针对人α/βT细胞受体上的一个单态性表位。与IgG2b同种型的抗CD3抗体不同,BMA 031能够在IgG2b低反应者的T细胞中诱导增殖反应。这种反应的发生与交联条件无关,这表明其激活模式不同于抗CD3抗体OKT3(IgG2a)的刺激,后者严格依赖于交联条件。为了进一步表征这两种抗体的刺激潜力,我们研究了对BMA 031和OKT3刺激有反应的淋巴细胞亚群。在CD45RA+细胞中,两种抗体表现出相似的效应。它们诱导白细胞介素-2受体(CD25)55-kDa链的弱表达,几乎没有白细胞介素-2分泌,但仍有强烈的增殖。在CD45R0+细胞中,OKT3和BMA 031表现出明显不同的效应。OKT3刺激强烈的CD25表达、强烈的白细胞介素-2产生和明显的增殖。相比之下,BMA 031刺激的CD45R0+细胞仅表现出弱的CD25表达,但既没有白细胞介素-2产生也没有增殖。这些数据表明,CD45RA+和CD45R0+细胞在通过CD3/T细胞受体复合物刺激时产生白细胞介素-2的能力以及对白细胞介素-2引发增殖反应的需求方面存在差异。OKT3和BMA 031在CD45R0+细胞中的差异效应可能是由于BMA 031未能触发白细胞介素-2产生,这可能是其无法在IgG2b低反应者中诱导CD3/T细胞受体交联的结果。因此,BMA 031是在这些个体中选择性激活CD45RA+细胞的有用工具。

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