Nature Immunology
3, 911 - 917 (2002)
Published online: 3 September 2002; | doi:10.1038/ni836
Staging and resetting T cell activation in SMACsBenjamin A. Freiberg1, 2, 6, Hannah Kupfer1, 6, William Maslanik1, Joe Delli1, 2, John Kappler3, Dennis M. Zaller4
& Abraham Kupfer1, 2, 51
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA. 2
Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. 3
Howard Hughes Medical Institute, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA. 4
Merck Research Labs, Rahway, NJ 07065, USA. 5
Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Abraham Kupfer kupfera@njc.orgDuring the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular signaling in SMACs by three-dimensional immunofluorescence microscopic localization of CD3, CD45, talin, phosphotyrosine, Lck and phosphorylated ZAP-70 in T cell−APC conjugates. Two distinct phases of spatial-temporal activation, one before and one after SMAC formation, which were separated by a brief state of inactivation caused by CD45, were observed at the T cell−APC contact area. We propose that pre-SMAC signals are sufficient to activate cell adhesion, but not productive T cell responses, which require orchestrated signaling in SMACs.
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