IMMUNOLOGICAL SYNAPSE ARRAYS: PATTERNED PROTEIN SURFACES THAT MODULATE IMMUNOLOGICAL SYNAPSE STRUCTURE FORMATION IN T CELLS
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SCOPUS
- Title
- IMMUNOLOGICAL SYNAPSE ARRAYS: PATTERNED PROTEIN SURFACES THAT MODULATE IMMUNOLOGICAL SYNAPSE STRUCTURE FORMATION IN T CELLS
- Authors
- Doh, J; Irvine, DJ
- Date Issued
- 2006-04-11
- Publisher
- NATL ACAD SCIENCES
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/12738
- DOI
- 10.1073/PNAS.0509404
- ISSN
- 0027-8424
- Article Type
- Article
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 103, no. 15, page. 5700 - 5705, 2006-04-11
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