CD28 Signals in the Immature Immunological Synapse
| Autor: | Abul K. Abbas, Douglas Dresnek, Matthew F. Krummel, Kimberly C. Howland, Samuel Edmondson, Pietro G. Andres |
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| Rok vydání: | 2004 |
| Předmět: |
Time Factors
CD3 Complex Ovalbumin T cell Immunology Antigen-Presenting Cells chemistry.chemical_element Mice Transgenic chemical and pharmacologic phenomena CHO Cells Cell Communication Biology Calcium Lymphocyte Activation Calcium in biology Immunological synapse Synapse Mice Adjuvants Immunologic CD28 Antigens T-Lymphocyte Subsets Cricetinae medicine Animals Immunology and Allergy Calcium Signaling Mice Knockout Antigen Presentation Mice Inbred BALB C T-cell receptor Histocompatibility Antigens Class II CD28 hemic and immune systems Peptide Fragments Cell biology Kinetics medicine.anatomical_structure chemistry Function (biology) Signal Transduction |
| Zdroj: | The Journal of Immunology. 172:5880-5886 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.10.5880 |
| Popis: | T cell recognition of peptide-MHC complexes on APCs results in the aggregation of TCRs at a central supramolecular activation complex (c-SMAC) within a mature immunological synapse. T cells require a second “costimulatory” signal for activation, the most important of which, for naive T cells, is from CD28. However the time at which CD28-derived signals are induced relative to c-SMAC formation is not well understood. In this study, we have assessed the kinetics of CD28 localization and function relative to well-established aspects of c-SMAC formation. CD28 accumulates at the immature synapse alongside the TCR and is likewise enriched at the synapse at the onset of the calcium signal. In addition, using CD28 deficient or reconstituted murine cells in a single-cell recording approach shows that CD28 regulates this signal within seconds of a TCR-mediated rise in intracellular calcium levels. Finally, CD28 exerts effects on both the initiation and stabilization of the synapse in parallel with its effects on the downstream proliferation of T cells. Together, the data show that CD28 functions in the immunological synapse before the formation of the c-SMAC. |
| Databáze: | OpenAIRE |
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