T cells respond not only to biochemical stimuli transmitted through their activating, costimulatory, and inhibitory receptors but also to biophysical aspects of their environment, including the receptors' spatial arrangement. While these receptors form nanoclusters that can either colocalize or segregate, the roles of these colocalization and segregation remain unclear. Deciphering these roles requires a nanoscale platform with independent and simultaneous spatial control of multiple types of receptors. Herein, using a straightforward and modular fabrication process, we engineered a tunable nanoscale chip used as a platform for T cell stimulation, allowing spatial control over the clustering and segregation of activating, costimulatory, and inhibitory receptors. Using this platform, we showed that, upon blocked inhibition, cells became sensitive to changes in the nanoscale ligand configuration. The nanofabrication methodology described here opens a pathway to numerous studies, which will produce an important insight into the molecular mechanism of T cell activation. This insight is essential for the fundamental understanding of our immune system as well as for the rational design of future immunotherapies.
© 2023 The Authors. Published by American Chemical Society.