Institute of Basic Medical Sciences, Beijing, PR China.
Int Immunopharmacol. 2010 Feb;10(2):200-6. doi: 10.1016/j.intimp.2009.10.016. Epub 2009 Nov 12.
Previous studies indicated that a partial T-cell receptor signal delivered by non-mitogenic anti-CD3 antibodies is critical for dampening the activated T-cell response. The mini-yCD3 is a novel non-mitogenic anti-CD3 antibody based on a murine anti-human CD3 antibody yCD3. However, the mechanism by which mini-yCD3 suppresses immune responses mediated by activated T-cells remains unknown. To elucidate its mechanism, we examined the effects of the mini-yCD3 on early signaling events in T-cells. Similar to the mitogenic anti-CD3 mAb, mini-yCD3 triggered changes in the T-cell receptor (TCR). However, unlike the mitogenic anti-CD3 stimulation, mini-yCD3 was ineffective at inducing the highly phosphorylated zeta chain and tyrosine phosphorylation of the associated tyrosine kinase ZAP-70. This proximal signaling deficiency failed to mobilize detectable Ca(2+) and translocate NF-AT into the nucleus. Additionally, the non-mitogenic anti-CD3 appeared insufficient for the redistribution of TCRs into an aggregated cap, which correlated with T-cell activation.
先前的研究表明，由非有丝分裂原性抗 CD3 抗体传递的部分 T 细胞受体信号对于抑制活化 T 细胞的反应是至关重要的。mini-yCD3 是一种新型的非有丝分裂原性抗 CD3 抗体，基于鼠抗人 CD3 抗体 yCD3。然而，mini-yCD3 抑制由活化 T 细胞介导的免疫反应的机制尚不清楚。为了阐明其机制，我们研究了 mini-yCD3 对 T 细胞早期信号事件的影响。类似于有丝分裂原性抗 CD3 mAb，mini-yCD3 触发了 T 细胞受体（TCR）的变化。然而，与有丝分裂原性抗 CD3 刺激不同，mini-yCD3 不能诱导高度磷酸化的 ζ 链和相关酪氨酸激酶 ZAP-70 的酪氨酸磷酸化。这种近端信号缺陷未能动员可检测的 Ca(2+)并将 NF-AT 易位到细胞核中。此外，非有丝分裂原性抗 CD3 似乎不足以使 TCR 重新分布到聚集的帽状结构中，这与 T 细胞激活相关。
