Abstract

The pre-T cell receptor complex regulates early T cell development and consists of a heterodimer of the TCR-β subunit in association with the pre-TCR-α chain. Notably, in contrast to α/β-expressing T cells, several studies suggested that the TCR-ζ chain is not stably associated with this pre-TCR complex. To examine the proximal signaling processes mediated by the pre-TCR complex and the role of the TCR-ζ chain in these processes, we stimulated pre-TCR-expressing cells and analyzed the interactions of the TCR/CD3 invariant chains with the Syk/ZAP-70 family of protein tyrosine kinases. Stimulation of the pre-TCR complex led to the tyrosine phosphorylation of the CD3∈ and TCR-ζ chains, as well as the phosphorylation and association of ZAP-70 and Syk with phosphorylated CD3∈ and TCR-ζ. These results demonstrate that the pre-TCR complex is functionally coupled to the TCR-ζ subunit and to the ZAP-70 and Syk protein tyrosine kinases.