한빛사논문
- 조회5,026
Abstract
*Department of Chemical Engineering and Department of Materials Science and Engineering, and Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139
Edited by Dan R. Littman, New York University Medical Center, New York, NY, and approved February 28, 2006 (received for review October 28, 2005)
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-
. 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.
Author contributions: J.D. and D.J.I. designed research; J.D. performed research; J.D. contributed new reagents/analytic tools; J.D. and D.J.I. analyzed data; and J.D. and D.J.I. wrote the paper.
Conflict of interest statement: No conflicts declared.
To whom correspondence should be addressed at: Massachusetts Institute of Technology, Room 8-425, 77 Massachusetts Avenue, Cambridge, MA 02139.
논문정보
- Research article
- 2006년 04월 (BRIC 등록일 )
- 국외 연구진
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