establishment of T cell polarity

Definition

Target type: biologicalprocess

The directed orientation of T cell signaling molecules and associated membrane rafts towards a chemokine gradient or a contact point with antigen presenting cell. [GOC:mgi_curators, PMID:11244041, PMID:12615889]

T cell polarity establishment is a crucial process that enables T cells to effectively respond to antigen presentation and mount an immune response. It involves the coordinated reorganization of the cell's cytoskeleton, membrane components, and signaling molecules to create a distinct front and back of the cell. This polarization allows T cells to focus their signaling and effector functions towards the target antigen, ultimately leading to the successful elimination of pathogens or infected cells.

The establishment of T cell polarity is initiated by the engagement of the T cell receptor (TCR) with its cognate antigen presented by an antigen-presenting cell (APC). This interaction triggers a cascade of intracellular signaling events that ultimately lead to the recruitment and activation of key polarity regulators, such as the small GTPases Cdc42 and Rac1. These molecules play a critical role in controlling cytoskeletal rearrangements, driving the formation of specialized cellular structures like the immunological synapse (IS) and the microtubule-organizing center (MTOC).

The IS is a specialized interface between the T cell and the APC, where the TCR and its associated signaling molecules cluster at the center of the contact zone. This clustering is mediated by interactions between transmembrane proteins on the T cell and the APC, as well as by cytoskeletal rearrangements driven by Cdc42 and Rac1. The IS serves as a platform for signal transduction, allowing the T cell to integrate information from the antigen and its environment.

Concomitant with IS formation, the MTOC, which is responsible for organizing and nucleating microtubules, relocates from the center of the cell to the periphery, typically towards the IS. This movement is driven by the polarized distribution of microtubule-associated proteins, which are regulated by the GTPase Rac1. The reorientation of the MTOC allows for the efficient transport of secretory vesicles containing effector molecules, such as cytokines and cytotoxic granules, towards the IS.

The establishment of T cell polarity is not a static process but rather a dynamic and highly regulated event. The precise spatial and temporal organization of the IS and MTOC is essential for the T cell to efficiently target its effector functions towards the APC and mount an effective immune response.

The disruption of T cell polarity can have detrimental effects on immune function, leading to impaired T cell activation, reduced effector responses, and even autoimmunity. Thus, understanding the molecular mechanisms underlying T cell polarity establishment is crucial for developing novel therapies targeting immune dysregulation and cancer.'
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Proteins (3)

Compounds (7)