J. Exp. Med., Volume 189, Number 7, April 5, 1999 1163-1168

ZAP-70 Protein Promotes Tyrosine Phosphorylation of T Cell Receptor Signaling Motifs (ITAMs) in Immature CD4⁺8⁺ Thymocytes with Limiting p56^lck

By Jennifer M. Ashe,^* David L. Wiest, Ryo Abe,^§ and Alfred Singer^*

From the ^* Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892;  Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and the ^§ Division of Immunobiology, Research Institute for Biological Sciences, Science University of  Tokyo, Chiba 278,  Japan

As a result of interaction with epithelial cells in the thymic cortex, immature CD4⁺8⁺ (double positive, DP) thymocytes express relatively few T cell receptors (TCRs) and contain diminished numbers of coreceptor-associated p56^lck (lck) PTK molecules. As a result, TCR signal transduction in DP thymocytes is significantly impaired, despite its importance for repertoire selection. We report here that, in DP thymocytes, tyrosine phosphorylation of TCR signaling motifs (ITAMs) by lck, an early event in TCR signal transduction, is dependent upon ZAP-70 protein independent of ZAP-70's kinase activity. Furthermore, the dependence on ZAP-70 protein for ITAM phosphorylation diminishes as available lck increases. Importantly, ZAP-70's role in ITAM phosphorylation in DP thymocytes is not limited to protecting phosphorylated ITAMs from dephosphorylation. Rather, this study indicates that ZAP-70 protein augments ITAM phosphorylation in DP thymocytes and so compensates in part for the relative deficiency of coreceptor-associated lck.

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