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Abstract

In this chapter we discuss the importance of micrometer- and nanometer-scale spatial structuring to cellular signaling in the immunological synapse – the contact region between an antigen-presenting cell (APC) and a T cell – focusing on the use of artificial biomimetic substrates. Immunological synapses cause the activation of T cells, which is a crucial stage in the adaptive immune response. Recent studies have investigated immunological synapse formation by bringing T cells into contact with surfaces that have been functionalized with peptide-MHC (p-MHC) and ICAM-1, which induce T cell activation and adhesion, respectively. Studies using p-MHC and ICAM-1-functionalized supported lipid bilayers have revealed important structures within the synapse at micrometer and nanometer length scales. Lithographically patterned substrates have been used to induce and control structure formation, providing controlled, realistic models of in vivo T cell activation. For example, lithographic walls have been used to confine laterally mobile protein molecules to micrometer-scale areas, mimicking possible effects of the APC cytoskeleton, and cells on lithographically patterned substrates have shown realistic segregation between p-MHC- and ICAM-1-binding membrane proteins. Similar investigations will soon be performed on the nanometer scale, most likely using block copolymer nanolithography, which enables surfaces to be patterned with precisely positioned single-protein molecules. Substrates patterned with single p-MHC molecules should enable investigation of the effect of p-MHC clustering on T cell activation. In addition to advancing our understanding of the immunological synapse, micro- and nanopatterned T cell-activating substrates could be used to provide improved T-cell phenotype control for adoptive T-cell therapies against cancer.