Dataset Information

TCR Signaling: Mechanisms of Initiation and Propagation.

ABSTRACT: The mechanisms by which a T cell detects antigen using its T cell antigen receptor (TCR) are crucial to our understanding of immunity and the harnessing of T cells therapeutically. A hallmark of the T cell response is the ability of T cells to quantitatively respond to antigenic ligands derived from pathogens while remaining inert to similar ligands derived from host tissues. Recent studies have revealed exciting properties of the TCR and the behaviors of its signaling effectors that are used to detect and discriminate between antigens. Here we highlight these recent findings, focusing on the proximal TCR signaling molecules Zap70, Lck, and LAT, to provide mechanistic models and insights into the exquisite sensitivity and specificity of the TCR.

SUBMITTER: Courtney AH

PROVIDER: S-EPMC5801066 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TCR Signaling: Mechanisms of Initiation and Propagation.

Courtney Adam H AH Lo Wan-Lin WL Weiss Arthur A

Trends in biochemical sciences 20171218 2

The mechanisms by which a T cell detects antigen using its T cell antigen receptor (TCR) are crucial to our understanding of immunity and the harnessing of T cells therapeutically. A hallmark of the T cell response is the ability of T cells to quantitatively respond to antigenic ligands derived from pathogens while remaining inert to similar ligands derived from host tissues. Recent studies have revealed exciting properties of the TCR and the behaviors of its signaling effectors that are used to ...[more]

PMID: 29269020

Similar Datasets

Project description:The two main pathological hallmarks of Parkinson's disease are loss of dopamine neurons in the substantia nigra pars compacta and proteinaceous amyloid fibrils composed mostly of ?-synuclein, called Lewy pathology. Levodopa to enhance dopaminergic transmission remains one of the most effective treatment for alleviating the motor symptoms of Parkinson's disease (Olanow, Mov Disord 34:812-815, 2019). In addition, deep brain stimulation (Bronstein et al., Arch Neurol 68:165, 2011) to modulate basal ganglia circuit activity successfully alleviates some motor symptoms. MRI guided focused ultrasound in the subthalamic nucleus is a promising therapeutic strategy as well (Martinez-Fernandez et al., Lancet Neurol 17:54-63, 2018). However, to date, there exists no treatment that stops the progression of this disease. The findings that ?-synuclein can be released from neurons and inherited through interconnected neural networks opened the door for discovering novel treatment strategies to prevent the formation and spread of Lewy pathology with the goal of halting PD in its tracks. This hypothesis is based on discoveries that pathologic aggregates of ?-synuclein induce the endogenous ?-synuclein protein to adopt a similar pathologic conformation, and is thus self-propagating. Phase I clinical trials are currently ongoing to test treatments such as immunotherapy to prevent the neuron to neuron spread of extracellular aggregates. Although tremendous progress has been made in understanding how Lewy pathology forms and spreads throughout the brain, cell intrinsic factors also play a critical role in the formation of pathologic ?-synuclein, such as mechanisms that increase endogenous ?-synuclein levels, selective expression profiles in distinct neuron subtypes, mutations and altered function of proteins involved in ?-synuclein synthesis and degradation, and oxidative stress. Strategies that prevent the formation of pathologic ?-synuclein should consider extracellular release and propagation, as well as neuron intrinsic mechanisms.

Dataset Information

TCR Signaling: Mechanisms of Initiation and Propagation.

Publications

TCR Signaling: Mechanisms of Initiation and Propagation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets