Staging and resetting T cell activation in SMACs.
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.
Freiberg
Benjamin A
BA
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA.
Kupfer
Hannah
H
Maslanik
William
W
Delli
Joe
J
Kappler
John
J
Zaller
Dennis M
DM
Kupfer
Abraham
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019000:Phosphotyrosine / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016608:Talin / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016608:Talin; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D017493:Leukocyte Common Antigens