1. ¹Institute for Biochemistry, Justus-Liebig-University, Medical Faculty, Friedrichstrasse 24, Giessen 35392, Germany
2. ²GSF, Research Center for Environment and Health, Institute of Toxicology, Ingolstädter Landstr. 1, Neuherberg 85764, Germany

Correspondence: ML Schmitz, Institute for Biochemistry, Justus-Liebig-University, Medical Faculty, Friedrichstrasse 24, Giessen 35392, Germany. Tel: +49 641 9947570; Fax: +49 641 9947589; E-mail: lienhard.schmitz@biochemie.med.uni-giessen.de; D Krappmann, GSF, Research Center for Environment and Health, Institute of Toxicology, Ingolstädter Landstr. 1, Neuherberg 85764, Germany. Tel: +49 89 3187 3461; Fax: +49 89 3187 3449; E-mail: Daniel.Krappmann@gsf.de

Received 30 September 2005; Revised 14 November 2005; Accepted 18 November 2005; Published online 13 January 2006.

Abstract

Full and productive activation of T lymphocytes relies on the simultaneous delivery of T cell receptor (TCR)- and coreceptor-derived signals. In naïve T cells engagement of the TCR alone causes anergy, while TCR triggering of preactivated T cells results in activation-induced cell death. Costimulatory signals are prominently mirrored by the activation of NF-B, which needs input from the TCR as well as from coreceptors in order to be fully activated and to fulfil its crucial function in the immune response. Coreceptor-generated signals tightly control the duration and amplitude of the NF-B response. The activation of IB kinase (IKK) complex at the contact zone between a T cell and an antigen-presenting cell offers the unique opportunity to study the spatial organization of IKK activation. Recent studies indicate that coreceptor pathways influence the threshold activities of many signalling mediators and thus act on multiple layers of the NF-B pathway.