National Academy of Sciences, Proceedings of the National Academy of Sciences, 4(118), 2021
Elsevier, Biophysical Journal, 3(120), p. 330a, 2021
DOI: 10.1016/j.bpj.2020.11.2077
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Significance The nanoscale organization of ligands and receptors is critical for cellular communication yet inherently challenging to investigate. We have here devised a DNA origami-based biointerface which allows the experimenter to adjust protein distances with nanometer precision as a means to enhance or disturb signaling while being responsive to large-scale reorganization processes during cell activation. Applying this biointerface to study the spatial requirements of T cell activation, we find that the smallest signaling-competent receptor unit consists of two stably ligated T cell receptors (TCRs) within a distance of 20 nanometers. Spatial organization of the physiological ligand pMHC, however, is not a relevant parameter of antigen-mediated T cell activation, as single, well-isolated pMHC molecules efficiently stimulate T cells.