Related Experiment Video
Updated: Jul 3, 2026
07:48
Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
1Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. cware@liai.org
Immunological Reviews
|July 11, 2008
Summary
Tumor necrosis factor (TNF)-related cytokines regulate immune responses. The herpesvirus entry mediator (HVEM) acts as a switch, balancing pro-inflammatory and inhibitory signals via B and T lymphocyte attenuator (BTLA) interactions, impacting T-cell activation and immune homeostasis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Cytokines are crucial for immune regulation, with tumor necrosis factor (TNF)-related cytokines and their receptors essential for lymphocyte activation.
- LIGHT, a member of the TNF superfamily, influences T-cell activation via herpesvirus entry mediator (HVEM) and the LT-beta receptor (LTbetaR).
Purpose of the Study:
- To investigate the signaling pathways involving HVEM, B and T lymphocyte attenuator (BTLA), and LTbetaR in immune regulation.
- To elucidate the role of HVEM as a molecular switch integrating distinct signaling pathways.
Main Methods:
- Analysis of cytokine-receptor interactions.
- Investigation of non-canonical binding sites and signaling mechanisms.
- Assessment of the integrated signaling circuit formed by LTbetaR and HVEM-BTLA pathways.
Main Results:
- A non-canonical binding site on HVEM for BTLA was identified, revealing an inhibitory signaling pathway.
- HVEM functions as a molecular switch, modulating between pro-inflammatory and inhibitory signals.
- The HVEM-BTLA pathway counteracts LTbetaR signaling, affecting dendritic cell proliferation.
Conclusions:
- The LTbetaR and HVEM-BTLA pathways form an integrated signaling circuit regulating immune responses.
- Targeting these pathways with antagonists or agonists offers potential therapeutic strategies for autoimmune diseases, infectious diseases, and cancer.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
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...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:24B Cell Activation and Differentiation
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...
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...