Tcr Downregulation
Tcr Downregulation - Related Videos
19:05
Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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Cited by 9 •
2015
This manuscript describes how to conduct (single molecule) Förster Resonance Energy Transfer (FRET)- based assays to measure the binding dynamics between T-cell antigen receptor (TCR) and antigenic peptide-loaded MHC molecules as they occur within the immunological synapse of a T-cell in contact with a functionalized planar supported lipid bilayer.
06:42
Identifying Kinase Inhibitors that Modulate the Thymocyte Response to Strong TCR Signals
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2025
In this video, we describe a method to identify the small-molecule kinase inhibitors that modulate the apoptosis of self-reactive CD4+CD8+ double-positive immature thymocytes. Apoptosis is induced in the double-positive thymocytes by activating them with anti-CD3- and anti-CD28-coated magnetic beads; this is followed by a small-molecule inhibitor treatment and flow cytometry analysis to detect if the inhibitors modulate the apoptotic marker expression.
01:15
Receptor Downregulation in MVBs
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2023
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded. The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
16:10
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
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Cited by 13 •
2012
The compartmentalization of proteins either within the plasma membrane or into intracellular locations is one regulatory mechanism that can greatly influence signaling outcomes; hence, to understand signaling it is important to study the spatial and temporal behavior of the proteins involved. We describe here a TIRF microscopy based system to study signal transduction in T cells, but is broadly applicable.
11:21
Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
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Cited by 3 •
2017
The current protocol combines single cell paired human TCR alpha and beta chain sequencing with streamlined generation of retroviral vectors compatible with in vitro and in vivo TCR expression.
FAQs
After sustained peptide-MHC engagement, TCR-associated signaling promotes receptor internalization from the plasma membrane. The complexes then move through endosomal compartments, intracellular sorting stations that determine their fate. Some receptors return to the cell surface through recycling, whereas others are directed toward degradation. This trafficking changes how many TCR complexes remain available to initiate or sustain signaling.
Sustained peptide-MHC engagement reduces the number of TCR complexes available at the cell surface. With fewer receptors positioned to respond, the T cell becomes less sensitive to continued antigenic stimulation. This reduction helps limit excessive immune activation while providing a mechanism through which ongoing antigen exposure can reshape the strength of T-cell signaling.
Recycling and degradation represent different trafficking outcomes for internalized TCR complexes. Recycling can return receptors to the cell surface, preserving or restoring the cell’s capacity to respond. Degradation removes receptors from future signaling availability for a longer-lasting reduction. Distinguishing these fates is therefore important when interpreting whether downregulation is transient or more sustained.
Measurements of TCR downregulation can indicate whether T cells have experienced antigen exposure and sustained activation. They provide information about changes in the surface receptor pool rather than serving only as a measure of receptor presence. Interpreted with other experimental observations, these measurements can help relate receptor loss to altered antigen sensitivity and immune regulation.
During persistent infections, researchers can use TCR downregulation as an indicator of continued antigen exposure and altered T-cell function. Comparing receptor levels under these conditions helps examine whether ongoing stimulation is associated with reduced signaling capacity or functional exhaustion. This makes the process relevant for connecting infection persistence with changes in adaptive immune responses.
Because receptor trafficking changes the number of TCR complexes available for signaling, TCR downregulation provides a framework for studying immune regulation. Investigators can use this process to examine how cellular responses might be limited or adjusted after continued stimulation. Such work is relevant to strategies designed to modulate T-cell activity without treating receptor abundance as a fixed property.