Related Experiment Video
Updated: Dec 20, 2025
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
7.8K
CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells
Ankita Mitra1, Sudarvili Shanthalingam1, Heather L Sherman1
1Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, United States.
Frontiers in Immunology
|May 28, 2020
Summary
Mature CD4 T cells express Notch ligands upon activation, regulating Notch signaling. CD28 signaling promotes ligand expression, while CD3 signaling inhibits it, revealing a novel regulatory mechanism.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Notch signaling is crucial for mammalian development and T cell function.
- Notch ligands (DLLs, JAGs) mediate signaling via trans-activation or cis-inhibition.
- The role of Notch ligands in purified CD4 T cell activation was previously unclear.
Purpose of the Study:
- To investigate Notch ligand expression on activated CD4 T cells.
- To elucidate the role of CD3 and CD28 signaling in Notch ligand regulation.
- To determine the impact of T cell-expressed Notch ligands on Notch activation.
Main Methods:
- Activation of mature CD4 T cells using anti-CD3/CD28 antibodies.
- Analysis of Notch ligand expression on T cell surfaces.
- Use of decoys to mimic Notch extracellular domain for cis-interaction studies.
Main Results:
- Mature CD4 T cells express Notch ligands early after activation.
- CD28 signaling induces ligand expression; CD3 signaling inhibits it.
- Expressed ligands (DLL1, DLL4, JAG1) cis-interact with Notch receptors, inhibiting activation.
Conclusions:
- Novel mechanism for regulating Notch ligand expression on CD4 T cells identified.
- T cell-expressed Notch ligands can cis-inhibit Notch activation.
- This provides new insights into T cell activation and regulation.
Related Concept Videos
03:14Notch Signaling Pathway
6.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.2K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.3K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.3K
01:22T Cell Activation and Clonal Selection
14.4K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
14.4K
02:54Canonical Wnt Signaling Pathway
10.2K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.2K
01:24B Cell Activation and Differentiation
15.6K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.6K
01:15Receptor Downregulation in MVBs
2.7K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.7K