Differential requirements for ZAP-70 in TCR signaling and T cell development

Theresa A. Kadlecek, Nicolai S C Van Oers, Leo Lefrancois, Sara Olson, Deborah Finlay, David H. Chu, Kari Connolly, Nigel Killeen, Arthur Weiss

Research output: Contribution to journalArticle

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Abstract

The Syk/ZAP-70 family of protein tyrosine kinases is indispensable for normal lymphoid development. Syk is necessary for the development of B cells and epithelial γδ T cells, whereas ZAP-70 is essential for the normal development of T cells and TCR signaling. In this study, we show that although development of the αβ lineage was arrested in the thymus, CD3- positive T cells, primarily of the γδ lineage, were present in the lymph nodes of mice lacking ZAP-70. Moreover, in the absence of ZAP-70, dendritic epidermal T cells were fewer in number and of abnormal morphology, and intestinal intraepithelial lymphocytes, normally containing a large proportion of γδ T cells, were markedly reduced. These data suggest that γδ T cells show a variable dependence upon ZAP-70 for their development. Biochemical analyses of thymocytes revealed a lack of basal ζ-chain tyrosine phosphorylation. However, several other substrates were inducibly tyrosine phosphoryiated following TCR stimulation. Thus, TCR-mediated signaling in ZAP-70-deficient thymocytes is only partially impaired. These studies suggest that Syk compensates only partially for the loss of ZAP-70, and that there is an absolute requirement of ZAP-70 for αβ T cells and epithelial γδ T cells, but not for some γδ T cells in peripheral lymphoid tissues.

Original languageEnglish (US)
Pages (from-to)4688-4694
Number of pages7
JournalJournal of Immunology
Volume161
Issue number9
StatePublished - Nov 1 1998

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T-Lymphocytes
Thymocytes
Tyrosine
ZAP-70 Protein-Tyrosine Kinase
Epithelial Cells
Lymphoid Tissue
Cell Lineage
Thymus Gland
B-Lymphocytes
Lymph Nodes
Phosphorylation
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Kadlecek, T. A., Van Oers, N. S. C., Lefrancois, L., Olson, S., Finlay, D., Chu, D. H., ... Weiss, A. (1998). Differential requirements for ZAP-70 in TCR signaling and T cell development. Journal of Immunology, 161(9), 4688-4694.

Differential requirements for ZAP-70 in TCR signaling and T cell development. / Kadlecek, Theresa A.; Van Oers, Nicolai S C; Lefrancois, Leo; Olson, Sara; Finlay, Deborah; Chu, David H.; Connolly, Kari; Killeen, Nigel; Weiss, Arthur.

In: Journal of Immunology, Vol. 161, No. 9, 01.11.1998, p. 4688-4694.

Research output: Contribution to journalArticle

Kadlecek, TA, Van Oers, NSC, Lefrancois, L, Olson, S, Finlay, D, Chu, DH, Connolly, K, Killeen, N & Weiss, A 1998, 'Differential requirements for ZAP-70 in TCR signaling and T cell development', Journal of Immunology, vol. 161, no. 9, pp. 4688-4694.
Kadlecek TA, Van Oers NSC, Lefrancois L, Olson S, Finlay D, Chu DH et al. Differential requirements for ZAP-70 in TCR signaling and T cell development. Journal of Immunology. 1998 Nov 1;161(9):4688-4694.
Kadlecek, Theresa A. ; Van Oers, Nicolai S C ; Lefrancois, Leo ; Olson, Sara ; Finlay, Deborah ; Chu, David H. ; Connolly, Kari ; Killeen, Nigel ; Weiss, Arthur. / Differential requirements for ZAP-70 in TCR signaling and T cell development. In: Journal of Immunology. 1998 ; Vol. 161, No. 9. pp. 4688-4694.
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