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01-06-2010 | Review

ZAP70: a master regulator of adaptive immunity

Authors: Alain Fischer, Capucine Picard, Karine Chemin, Stéphanie Dogniaux, Françoise le Deist, Claire Hivroz

Published in: Seminars in Immunopathology | Issue 2/2010

Abstract

The protein tyrosine kinase ZAP70 became the subject of intense scrutiny in the early nineties, when ZAP70 mutations were characterized in several young patients presenting with severe T cell immunodeficiencies. The association of a lack of expression of ZAP70 with an immunodeficiency consisting in a markedly reduced T lymphocyte-mediated immunity highlighted the crucial role of this tyrosine kinase in T cell development and function. This discovery was soon accompanied by the characterization of the substrates of ZAP70 and the signalling cascades that depend on ZAP70 activity. These studies demonstrated that ZAP70 was indeed at the crossroad of several signalling pathways that control T lymphocyte development and function. Recently, a revival of interest for this protein came again from studies associating abnormal ZAP70 expression with pathological conditions. Some chronic lymphocytic leukemia B cells were shown to express ZAP70, and this expression was correlated with bad prognosis. Mouse models also revealed that partial defects in ZAP70 activity can be associated with autoimmunity. These last results suggested that ZAP70 is involved in the fine balance between immunity and tolerance. In this review, we will discuss the role of ZAP70 in T cell activation and focus on what we learnt from pathological conditions associated with defective expression or activity of the ZAP70 kinase.

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Title: ZAP70: a master regulator of adaptive immunity
Authors: Alain Fischer
Capucine Picard
Karine Chemin
Stéphanie Dogniaux
Françoise le Deist
Claire Hivroz
Publication date: 01-06-2010
Publisher: Springer-Verlag
Published in: Seminars in Immunopathology / Issue 2/2010
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-010-0196-x

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