Tcr Signaling
Tcr Signaling - Related Videos
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.
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.
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.
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.
01:26
Signal and System
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2024
A signal x(t) is a set of data or a time function representing a variable of interest. Signals typically convey information about a phenomenon, such as atmospheric temperature, humidity, human voice, television images, a dog's bark, or birdsongs. More generally, a signal can be a function of more than one independent variable. For instance, images depend on horizontal and vertical positions and can be regarded as two-dimensional signals. However, this text will focus on one-dimensional signals...
FAQs
Engagement brings CD4 or CD8 coreceptors, together with the kinase Lck, to the receptor complex. Lck phosphorylates immunoreceptor tyrosine-based activation motifs, or ITAMs, within CD3. These phosphorylated sites recruit ZAP-70, a signaling kinase that propagates the receptor-generated signal into downstream pathways. This early phosphorylation and recruitment sequence links antigen recognition to intracellular T-cell activation.
LAT and SLP-76 organize signaling components after ZAP-70 activation, helping connect proximal receptor events with several major response pathways. Their activity supports calcium-dependent activation of NFAT, Ras–MAPK signaling leading to AP-1, and NF-κB activation. By coordinating these routes, the signaling complex enables T cells to produce cytokines, proliferate, and undergo functional differentiation.
The calcium–NFAT pathway, Ras–MAPK–AP-1 pathway, and NF-κB pathway represent coordinated branches of the same receptor-triggered response. Together, they regulate gene-expression programs associated with cytokine production, proliferation, and differentiation. Considering these pathways as an integrated network is important because T-cell responses depend on their combined activity rather than on a single downstream signal.
CD4 and CD8 coreceptors help position Lck at the T-cell receptor complex when the receptor engages peptide–MHC. This placement enables phosphorylation of CD3 ITAMs and supports ZAP-70 recruitment. Their participation therefore connects recognition of peptide–MHC with the earliest intracellular signaling events, helping initiate the pathways required for an effective T-cell response.
A useful conceptual sequence begins with peptide–MHC engagement, followed by coreceptor-associated Lck activity, CD3 ITAM phosphorylation, and ZAP-70 recruitment. Analysis then tracks LAT and SLP-76, followed by calcium–NFAT, Ras–MAPK–AP-1, and NF-κB pathway activation. Finally, investigators relate these signaling events to cytokine production, proliferation, differentiation, or other T-cell responses.
These studies show how antigen recognition is converted into T-cell responses that contribute to adaptive immunity and infection control. Examining the signaling steps and resulting cytokine production, proliferation, and differentiation can clarify how immune responses develop against pathogens. That information provides a mechanistic basis for investigating vaccine design and understanding how antigen-driven cellular immunity is regulated.
TCR signaling controls core features of T-cell activity, including activation, proliferation, differentiation, and cytokine production. Consequently, studying this pathway can inform immunotherapy development by clarifying how T-cell responses are generated and regulated. The same framework helps investigate autoimmune disorders, in which immune activity is misdirected, and immunodeficiency disorders, in which effective responses may be impaired.