Abstract
The immune synapse (IS) is a well-known intercellular communication platform, organized at the interphase between the antigen presenting cell (APC) and the T cell. After T cell receptor (TCR) stimulation, signaling from plasma membrane proteins and lipids is amplified by molecules and downstream pathways for full synapse formation and maintenance. This secondary signaling event relies on intracellular reorganization at the IS, involving the cytoskeleton and components of the secretory/recycling machinery, such as the Golgi apparatus and the endolysosomal system (ELS). T cell activation triggers a metabolic reprogramming that involves the synthesis of lipids, which act as signaling mediators, and an increase of mitochondrial activity. Then, this mitochondrial activity results in elevated reactive oxygen species (ROS) production that may lead to cytotoxicity. The regulation of ROS levels requires the concerted action of mitochondria and peroxisomes. In this review, we analyze this reprogramming and the signaling implications of endolysosomal, mitochondrial, peroxisomal, and lipidic systems in T cell activation.
Highlights
Cellular adaptive immunity requires the interaction of antigen presenting cells (APC) with T cells bearing T cell receptors (TCR), which need to be specific for the antigen: major histocompatibility complex (MHC) combination presented by the APC
In this review we offer to the reader an overview of the changes in intracellular organelles and lipid metabolism associated to T cell activation through the immune synapse (IS)
Mitochondrial metabolism is critical for T cell activation through production of mitochondrial reactive oxygen species (ROS) [54,55,56]
Summary
Cellular adaptive immunity requires the interaction of antigen presenting cells (APC) with T cells bearing T cell receptors (TCR), which need to be specific for the antigen: major histocompatibility complex (MHC) combination presented by the APC. The T lymphocyte relocates receptors, cytoskeletal components, and specific organelles to the contact site with the APC These drive actin polymerization and reorganization, forming a contractile actomyosin ring that shapes the IS [6,7]. As a result of these transport events the plasma membrane has a heterogeneous profile composed of co-existing domains enriched in different proteins and lipids These may serve to regulate cell-to-cell communication and activation [26]. This process requires high ATP consumption that results in an increase of lipid and ROS levels These changes in the T cell modulate plasma membrane composition, protein signaling pathways and cytoskeleton organization. These effects are accompanied by changes in metabolic processes that, in turn, regulate ROS levels.
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