CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization

Eur J Immunol. 2008 Jan;38(1):40-7. doi: 10.1002/eji.200737423.


CTLA-4 is a co-receptor that modulates the threshold of T cell activation and autoimmunity. We previously showed that CTLA-4 reverses the TCR-mediated stop signal needed for T cell/APC interactions [Schneider et al., Science 2006, 313: 1972]. In this study, using a different T cell system, we show that CTLA-4 expression changed the behavior of T8.1 T cells by reducing the contact time between T cell and APC, preventing re-inforced contacts, and reducing the contact area at the immunological synapse. This led to a major reduction in Ca(2+) influx/mobilization and interleukin-2 production. Further, anti-CD3/CTLA-4 increased T cell motility on antibody-coated glass slides, concurrent with an abrogation of ZAP70 microcluster formation. Our findings further support a role for CTLA-4 in limiting the interaction between T cell and APC that is needed for optimal activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation / metabolism
  • CTLA-4 Antigen
  • Calcium / metabolism*
  • Cell Adhesion / immunology
  • Cell Communication / immunology
  • Cell Movement / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Mice
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / metabolism*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Calcium