Meeting report: Signal transduction meets systems biology

As cellular constituents of the adaptive immune system, T cells carry an individual T cell antigen receptor (TCR)/CD3 complex with which they recognize specific antigens, resulting in activation of the cell and the mounting of an immune response [1,2]. However, to initiate a successful immune response against pathogens, without creating an inappropriate response against self-antigens, T cells have to discriminate between healthy cells of the body and diseased or infected cells. It is thought that the affinity of antigens to the TCR/CD3 complex governs this discrimination during intrathymic development. In the periphery, infected and diseased cells will present specific ‘foreign’ antigens with high affinity to the TCR leading to activation of the T cell. Due to the selection process, peripheral self-antigens have low or no binding-affinity and should not result in T-cell activation, but might rather be involved in T-cell survival. If the multiple backup systems of central and peripheral tolerance fail, T cells with high affinity to self-antigens might cause autoimmunity.T-cell activation is a complex process relying on multiple layers of tightly controlled intracellular signalling modules that form an intricate network. In order to gain systems-level insight into critical modules of the network and finally into the behaviour of the complete network, the SYBILLA consortium was founded. It groups 18 partners from 9 different EU countries, including a management company (Novamen, Lyon, France; represented by Sandrine Rival in SYBILLA), and coordinated by Wolfgang Schamel (Freiburg, Germany). Detailed information can be found at http://www.sybilla-t-cell.de webcite.The current development of several ongoing projects has been reported at the meeting and will be described below. In essence, through a multidisciplinary effort, SYBILLA aims to understand at the systems level, how T-cells discriminate foreign from auto-antigens, how T cells differentiate from naive cells into