Qualitatively distinct signaling through T cell antigen receptor subunits

被引:34
作者
Jensen, WA
Pleiman, CM
Beaufils, P
Wegener, AMK
Malissen, B
Cambier, JC
机构
[1] NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DIV BASIC SCI,DENVER,CO 80206
[2] CNRS MARSEILLE LUMINY,INSERM,CTR IMMUNOL,MARSEILLE,FRANCE
关键词
T cell receptor; immunoreceptor tyrosine-based activation motif; signaling; calcium; phospholipase C gamma 1;
D O I
10.1002/eji.1830270320
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell antigen receptors (TCR) contain several subunits including CD3 gamma, delta, and epsilon, and TCR zeta and eta which are capable of mediating signal transduction. It is unclear whether the signaling function of these subunits is completely redundant. To assess the relative signaling capabilities of TCR subunits, we compared proximal events in signal transduction by wild-type TCR complexes and TCR devoid of functional zeta subunits, as well as chimeric receptors containing the cytoplasmic domains of TCR zeta; or CD3 epsilon. Results demonstrate that in BW5147 wild-type TCR, tail-less zeta TCR, CD3 epsilon, and TCR zeta transduce signals leading to tyrosine phosphorylation of similar sets of cellular substrates, including the receptor subunits, Fyn, ZAP-70, and phospholipase C gamma 1 (PLC gamma 1). Surprisingly, unlike wild-type TCR, tail-less zeta TCR, and CD3E, TCRj was incapable of transducing signals resulting in inositol triphosphate (IP3) generation or intracellular free calcium ([Ca2+](i)) mobilization. These data indicate that tyrosine phosphorylation of PLC gamma 1 is not sufficient to drive IP3 production and [Ca2+](i) mobilization. Most importantly, data presented indicate that TCR zeta and CD3 epsilon engage partially distinct signaling pathways.
引用
收藏
页码:707 / 716
页数:10
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