TY - JOUR
T1 - Staging and resetting T cell activation in SMACs
AU - Freiberg, Benjamin A.
AU - Kupfer, Hannah
AU - Maslanik, William
AU - Delli, Joe
AU - Kappler, John
AU - Zaller, Dennis M.
AU - Kupfer, Abraham
N1 - Funding Information:
Acknowledgments We thank P. Marrack,A.Weiss and G. Koretzky for helpful comments and T. Potter for critical reading of the manuscript. Supported in part by grants from the NIH (to A. K.).
PY - 2002/10
Y1 - 2002/10
N2 - During 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.
AB - During 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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U2 - 10.1038/ni836
DO - 10.1038/ni836
M3 - Article
C2 - 12244310
AN - SCOPUS:0036794399
VL - 3
SP - 911
EP - 917
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 10
ER -