Seminars in Immunopathology

, Volume 32, Issue 2, pp 107–116 | Cite as

ZAP70: a master regulator of adaptive immunity

  • Alain Fischer
  • Capucine Picard
  • Karine Chemin
  • Stéphanie Dogniaux
  • Françoise le Deist
  • Claire Hivroz


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.


Immunodeficiency Autoimmunity Tyrosine kinase Immunoreceptor 


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Alain Fischer
    • 1
    • 2
    • 3
  • Capucine Picard
    • 3
    • 4
    • 5
  • Karine Chemin
    • 6
    • 7
  • Stéphanie Dogniaux
    • 6
    • 7
  • Françoise le Deist
    • 8
  • Claire Hivroz
    • 6
    • 7
  1. 1.INSERM, U768, Hôpital Necker-Enfants MaladesParisFrance
  2. 2.Unité d’Immuno-Hématologie Pédiatrique, Assistance Publique-Hôpitaux de ParisHôpital Necker-Enfants MaladesParisFrance
  3. 3.Faculté NeckerUniversité Paris DescartesParisFrance
  4. 4.Centre d’Étude des Déficits Immunitaires, Assistance Publique-Hôpitaux de ParisHôpital Necker-Enfants MaladesParisFrance
  5. 5.Génétique Humaine des Maladies Infectieuses, Faculté NeckerINSERM, Unité 550ParisFrance
  6. 6.Centre de RechercheInstitut CurieParisFrance
  7. 7.Immunité et CancerINSERM, Unité 932ParisFrance
  8. 8.Department of Microbiology and Immunology, and Centre of Research, CHU Sainte-JustineUniversité de MontréalMontrealCanada

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