title: TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction.
abstract: TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These pre-existing microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs.
authors.affiliation: Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Crites
authors.affiliation: Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Kartika
authors.initials: K
authors.lastname: Padhan
authors.affiliation: Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016; Department of Pathology, New York University School of Medicine, New York, NY 10026;
authors.forename: James
authors.initials: J
authors.lastname: Muller
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10026; New York University Cancer Institute, New York University School of Medicine, New York, NY 10026; and.
authors.forename: Michelle
authors.initials: M
authors.lastname: Krogsgaard
authors.affiliation: Optical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Fort Detrick, Frederick, MD 21702.
authors.forename: Prabhakar R
authors.initials: PR
authors.lastname: Gudla
authors.affiliation: Optical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Fort Detrick, Frederick, MD 21702.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lockett
authors.affiliation: Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; rajat.varma@nih.gov.
authors.forename: Rajat
authors.initials: R
authors.lastname: Varma
mesh_terms: D000818:Animals; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse