Related Experiment Video
Updated: Jul 10, 2026
10:13
Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability
Tsvetelina Pentcheva-Hoang1, Lieping Chen, Drew M Pardoll
1Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Summary
Programmed death-1 (PD-1) localizes to the T cell synapse, particularly with dendritic cells expressing high B7-DC. Its accumulation kinetics resemble CD28, suggesting cytoskeletal involvement in T cell inhibition.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Programmed death-1 (PD-1) is crucial for T cell inhibition.
- Intracellular trafficking and synapse localization of PD-1 remain largely unknown.
Purpose of the Study:
- To investigate the intracellular trafficking of PD-1 in activated T cells.
- To determine the requirements for PD-1 localization to the immunological synapse.
- To understand the role of B7-DC and B7-H1 ligands in PD-1-mediated T cell regulation.
Main Methods:
- Analysis of PD-1 localization in activated T cells using microscopy.
- Investigating T cell interactions with dendritic cells (DCs) expressing varying levels of B7-DC and B7-H1.
- Assessing cytokine secretion upon T cell restimulation.
Main Results:
- PD-1 localizes to the plasma membrane, Golgi, and trans-Golgi network in activated T cells.
- PD-1 accumulates extensively at the T cell-DC synapse when DCs express high B7-DC.
- B7-H1 is also important, especially when B7-DC is low, influencing cytokine secretion.
- PD-1 and CD28 exhibit similar synaptic accumulation kinetics, linked to cytoskeletal reorganization and ligand binding.
Conclusions:
- PD-1 trafficking and synapse localization are regulated by specific ligand interactions on dendritic cells.
- Cytoskeletal reorganization plays a role in PD-1's accumulation at the immunological synapse.
- Understanding PD-1 dynamics provides insights into T cell regulation and immune responses.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
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...