Our adaptive immune system has evolved to be able to distinguish our own cells from foreign material such as viruses and bacteria, and to protect us from the latter. This is possible thanks to an elaborate system of different cells and molecular pathways in the adaptive immune system. An important step is the triggering of T cells to start an immune response, which takes place when a T cell contacts an antigen presenting cell. However, how this is controlled by different membrane proteins and the molecular interactions involved to initiate an adaptive immune response are for many instances lacking. We are currently investing this problem by studying the organisation of key molecules, such as CD45, TCR, CD4 and pMHC, on the surface of T cells and antigen presenting cells during the early stages of an immune response. This is achieved by using artificial cell surfaces, so called supported lipid bilayers (SLBs), and advanced fluorescence microscopy with fluorescence labelling of the studied molecules (see Fig. 1). By using SLBs it is possible to replace one of the cells in the contact with an artificial cell membrane, the SLB, which can be made to contain a well-controlled mix of the membrane proteins that are investigated. This approach was recently used by me and collaborators to study how exclusion of the long phosphatase CD45 from SLB/T-cell contacts can initiate T-cell signalling without any antigens,^1,2 and how the model membrane itself can induce signaling.³ We are also using these systems to measure two-dimensional binding kinetics of various protein-protein interactions between cells in the adaptive immune system. Examples of this includes measuring the extremely weak interaction between the immune cell proteins CD4 and pMHC class II,⁴ and we have also shown how auxiliary binding molecules can both increase and decrease the apparent affinity of TCR to pMHC depending on the relative protein densities.⁵ We have also recently developed a method making it possible to measure the binding affinity on single cells making it possible to study binding differences within the cell population.⁶ All together, we aim to get a better understanding of how the immune system is triggered, and a deeper knowledge of how it can separate our own cells from foreign material.