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 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.
Lv
Ming
M
Institute of Basic Medical Sciences, Beijing, PR China.
Qiao
Chunxia
C
Lin
Zhou
Z
Yu
Ming
M
Hou
Chunmei
C
Sun
Yingxun
Y
Li
Yan
Y
Feng
Jiannan
J
Shen
Beifen
B
D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D015220:Calcium Channels / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008934:Mitogens / Q000009:adverse effects / Q000276:immunology; D050778:NFATC Transcription Factors / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology
D017252:CD3 Complex; D015220:Calcium Channels; D007166:Immunosuppressive Agents; D008934:Mitogens; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; D051746:ZAP-70 Protein-Tyrosine Kinase