1. CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization
- Author
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Hebin Liu, Christopher E. Rudd, Georges Bismuth, Helga Schneider, and Xin Smith
- Subjects
Cell signaling ,T-Lymphocytes ,T cell ,Immunology ,Antigen-Presenting Cells ,chemical and pharmacologic phenomena ,Cell Communication ,Biology ,Lymphocyte Activation ,Article ,Calcium in biology ,Immunological synapse ,Mice ,Antigens, CD ,Cell Movement ,Cell Adhesion ,medicine ,Animals ,Humans ,Immunology and Allergy ,CTLA-4 Antigen ,Antigen-presenting cell ,Cell adhesion ,ZAP-70 Protein-Tyrosine Kinase ,ZAP70 ,hemic and immune systems ,Antigens, Differentiation ,Cell biology ,medicine.anatomical_structure ,CTLA-4 ,Calcium - Abstract
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.
- Published
- 2008