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Immunological synapse arrays: Patterned protein surfaces that modulate immunological synapse structure formation in T cells

Cited 150 time in Web of Science Cited 151 time in Scopus
Authors

Doh, J; Irvine, DJ

Issue Date
2006-04
Publisher
National Academy of Sciences
Citation
Proceedings of the National Academy of Sciences of the United States of America, Vol.103 No.15, pp.5700-5705
Abstract
T cells are activated by recognition of foreign peptides displayed on the surface of antigen presenting cells (APCs), an event that triggers assembly of a complex microscale structure at the T cell-APC interface known as the immunological synapse (IS). It remains unresolved whether the unique physical structure of the synapse itself impacts the functional response of T cells, independent of the quantity and quality of ligands encountered by the T cell. As a first step toward addressing this question, we created multicomponent protein surfaces presenting lithographically defined patterns of tethered T cell receptor (TCR) ligands (anti-CD3 "activation sites") surrounded by a field of tethered intercellular adhesion molecule-1 (ICAM-1), as a model substrate on which T cells could be seeded to mimic T cell-APC interactions. CD4(+) T cells seeded on these surfaces polarized and migrated; on contact with activation sites, T cells assembled an IS with a structure modulated by the physical pattern of ligand encountered. On surfaces patterned with focal spots of TCR ligand, T cells stably interacted with activation sites, proliferated, and secreted cytokines. In contrast, T cells interacting with activation sites patterned to preclude centralized clustering of TCR ligand failed to form stable contacts with activation sites, exhibited aberrant PKC-theta clustering in a fraction of cells, and had significantly reduced production of IFN-gamma. These results suggest that focal clustering of TCR ligand characteristic of the "mature" IS may be required under some conditions for full T cell activation.
ISSN
0027-8424
URI
https://hdl.handle.net/10371/203501
DOI
https://doi.org/10.1073/pnas.0509404103
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  • College of Engineering
  • Department of Materials Science & Engineering
Research Area Ex Vivo Models, Lymphocyte Biology, Smart Biomaterials

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