Abstract
The immunological synapse is the molecular platform for signal integration that controls T cell activation in response to antigen presentation. Interleukin 2 (IL-2) is an essential signal for effective T cell activation and proliferation after T cell receptor (TCR) engagement. However, the molecular mechanisms that link IL-2 signaling with TCR activation are not fully understood. Here, we investigate the spatial and temporal relationship between the IL-2 receptor (IL-2R) and the TCR function by visualizing their localization and activity during the formation of a synaptic contact. We use a supported lipid bilayer (SLB) system to mimic the surface of a virus-infected cell and we visualize antigen-specific CD8+ T cells forming a contact with it. The SLB system allows us to manipulate the two-dimensional accessibility of IL-2R and TCR ligands at the contact. For this purpose, we use the novel biologic therapeutics Immuno-STATs™. The full Immuno-STATs™ framework consists of a Fc-formatted peptide-HLA complex and a modified IL-2 with reduced affinity. Using structural variants of these compounds, we can manipulate the spatial link between IL-2 and TCR signaling pathways and evaluate its relevance for an efficient synapse formation. Our data sheds light into the mechanisms of early IL-2 action and IL-2R assembly during the immunological synapse.
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