Signal initiation in T-cell receptor microclusters
Maria-Cristina Seminario
Department of Pathology, Tufts University School of Medicine, Boston, MA, USA
Search for more papers by this authorStephen C. Bunnell
Department of Pathology, Tufts University School of Medicine, Boston, MA, USA
Search for more papers by this authorMaria-Cristina Seminario
Department of Pathology, Tufts University School of Medicine, Boston, MA, USA
Search for more papers by this authorStephen C. Bunnell
Department of Pathology, Tufts University School of Medicine, Boston, MA, USA
Search for more papers by this authorStephen C. Bunnell
Department of Pathology
Tufts University Medical School
Jaharis Bldg., Rm. 512
150 Harrison Ave.
Boston, MA 02111, USA
Tel.: +1 617 636 2174
Fax: +1 617 636 2990
e-mail: [email protected]
Abstract
Summary: Although dynamic imaging technologies have provided important insights into the underlying processes responsible for T-cell activation, the processes that link antigen recognition to downstream signaling remain poorly defined. Converging lines of inquiry indicate that T-cell receptor (TCR) microclusters are the minimal structures capable of directing effective TCR signaling. Furthermore, imaging studies have determined that these structures trigger the assembly of oligomeric signaling scaffolds that contain the adapters and effectors required for T-cell activation. Existing models of T-cell activation accurately explain the sensitivity and selectivity of antigen recognition. However, these models do not account for important properties of microclusters, including their peripheral formation, size, and movement on the actin cytoskeleton. Here we examine how lipid rafts, galectin lattices, and protein scaffolds contribute to the assembly, function, and fate of TCR microclusters within immune synapses. Finally, we propose a ‘mechanical segregation’ model of signal initiation in which cytoskeletal forces contribute to the lateral segregation of molecules and cytoskeletal scaffolds provide a template for microcluster assembly.
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