immunological synapse

Definition

Target type: cellularcomponent

An area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell formed through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and the target cell and facilitating activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction. [GOC:mgi_curators, PMID:11244041, PMID:11376300]

The immunological synapse (IS) is a specialized cell-cell junction formed between an antigen-presenting cell (APC), such as a dendritic cell or macrophage, and a T lymphocyte. It facilitates the efficient transfer of information between these cells, crucial for the initiation of an adaptive immune response. This intricate structure is characterized by a distinct spatial organization of molecular components, divided into concentric rings:

1. **The central supramolecular activation cluster (cSMAC):** This central zone is enriched in TCRs, CD4/CD8 co-receptors, and signaling molecules like Lck and ZAP70. TCR engagement with MHC-peptide complexes on the APC triggers signal transduction pathways, ultimately leading to T cell activation.

2. **The peripheral supramolecular activation cluster (pSMAC):** Surrounding the cSMAC, the pSMAC is enriched in adhesion molecules like LFA-1 (on the T cell) and ICAM-1 (on the APC). These molecules mediate the stable adhesion between the two cells, ensuring prolonged contact and efficient signal transfer.

3. **The distal supramolecular activation cluster (dSMAC):** This outermost ring is characterized by the presence of cytoskeletal components, such as actin and microtubules. These structures play a role in the polarization of the T cell towards the APC, enabling the efficient delivery of signaling molecules to the cSMAC.

The formation and function of the IS are highly regulated processes. The initial contact between the T cell and the APC involves transient interactions. Upon TCR recognition of MHC-peptide complexes, the cSMAC forms, followed by the recruitment of signaling molecules and the assembly of the pSMAC. The dSMAC then establishes a polarized cytoskeleton, ensuring the stability and functionality of the synapse.

Within the IS, various cellular components contribute to the efficient communication between the APC and the T cell:

- **Signaling molecules:** Key signaling molecules, including tyrosine kinases (Lck, ZAP70), adaptor proteins (LAT, SLP-76), and phospholipases (PLCγ), are recruited to the cSMAC. These molecules initiate downstream signaling pathways, leading to T cell activation, proliferation, and differentiation.

- **Adhesion molecules:** LFA-1/ICAM-1 interactions are crucial for the stable adhesion between the two cells. These interactions strengthen the synapse, ensuring prolonged contact and efficient signaling.

- **Cytoskeletal components:** Actin and microtubules are essential for the organization and polarization of the T cell towards the APC. They facilitate the delivery of signaling molecules to the cSMAC, enabling the efficient transfer of information between the cells.

- **Vesicles:** Exocytosis and endocytosis play important roles in the IS. Exocytosis delivers molecules like cytokines and chemokines to the synapse, while endocytosis regulates the internalization of MHC-peptide complexes, ensuring the efficient clearance of antigens.

- **Lipids:** Specific lipid species, including phosphatidylinositol 4,5-bisphosphate (PIP2) and ceramide, are localized within the IS. These lipids contribute to the clustering of signaling molecules and the organization of the synapse.

The formation and function of the IS are tightly regulated by a complex interplay between various cellular components, ensuring the efficient initiation and execution of an adaptive immune response. The IS serves as a platform for T cell activation and differentiation, leading to the elimination of pathogens and the establishment of immunological memory.
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Proteins (14)

Compounds (418)