Duration of antigen receptor signaling determines T-cell tolerance or activation
Year: 2010
Type: article
Abstract: The early events that determine the decision between lymphocyte tolerance and activation are not well-understood. Using a model of systemic self-antigen recognition by CD4(+) T cells, we show, using single-cell biochemical analyses, that tolerance is characterized by transient signaling events downstream of T-cell receptor engagement in the mammalian target of rapamycin (mTOR) and NF-κB pathways. Parallel studies done by live cell imaging show that the key difference between tolerance and activation is the duration of the T cell-antigen presenting cell (APC) interaction, as revealed by stable T-cell immobilization on antigen encounter. Brief T cell-APC interactions result in tolerance, and prolonged interactions are associated with activation and the development of effector cells. These studies show that the duration of T cell-APC interactions and magnitude of associated TCR-mediated signaling are key determinants of lymphocyte tolerance vs. activation.
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1893893447, G2475776325, Spatiotemporal Control of T cell Synapse Stabilization and Signaling, Immune Tolerance and Autoimmunity, Immunodeficiency and Autoimmunity, G5510168712, Autoimmunity Center of Excellence, The Role of DC's Tolerance, G8343853698, Understanding Influenza and SARS-CoV-2 vaccine responses, in vivo and in vitro
OpenAlex ID: W2063821602