Impact of accessory receptors on close-contact formation and ligand discrimination by T cells (360G-Wellcome-203737_Z_17_A)

The immune system of vertebrates has evolved a remarkable ability to adapt to new pathogens. The ability of T cells to discriminate between self and foreign antigen is crucial for adaptive immune responses. However, we do not fully understand the mechanism behind T cell activation. Interactions between TCR and other surface molecules are responsible for activation at the interface between T cell and antigen-presenting cell (APC). Unlike previously thought, this interface is not just two flat membrane surfaces, but the T cell engages the APC with numerous small membrane protrusions, that form microdomains called close contacts. We hypothesise that the temporal and spatial properties of those microdomains are important for antigen discrimination. We will measure the effect of accessory receptors on the proximal signalling indirectly by stimulation assays in combination with mathematical modelling. Furthermore, we investigate close contacts directly my microscopy, measuring properties like size, distribution and movement. We believe our results will improve the comprehension of T cell activation, a process central for the defence against invading pathogens and cancer and the prevention of autoimmunity.