Immunological Synapse Arrays: Patterned Protein Surfaces That Modulate Immunological Synapse Structure Formation in T Cells.
From: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Apr 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 15
- Pages: 5700-5
- Medium: Print
- Language: English
- Citation (JAMA): Doh Junsang, Irvine Darrell J, et al. Immunological Synapse Arrays: Patterned Protein Surfaces That Modulate Immunological Synapse Structure Formation in T Cells.. Proc. Natl. Acad. Sci. U.S.A. Apr 2006;103:5700-5
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- 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.
Mesh Headings (Keywords): Animals, Antigen-Presenting Cells, Antigens, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 16585528
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