The novel non-mitogenic anti-CD3 antibody, mini-yCD3, delivers a partial TCR signal

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 ζ chain and tyrosine phosphorylation of the associated tyrosine kinase ZAP-70. This proximal signaling deficiency failed to mobilize detectable Ca2+ 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.