VLA-4

VLA-4 (Very Late Antigen-4) is an integrin found on the surface of leukocytes. It is a receptor for fibronectin and VCAM-1 (vascular cell adhesion molecule-1), and plays a crucial role in the adhesion and migration of leukocytes.

Etymology

The term "VLA-4" stands for "Very Late Antigen-4". The name is derived from the fact that this antigen is expressed at a very late stage of T cell activation.

Structure

VLA-4 is a heterodimeric protein composed of two subunits: α4 (CD49d) and β1 (CD29). The α4 subunit is unique to VLA-4, while the β1 subunit is shared with other integrins.

Function

VLA-4 mediates the adhesion of leukocytes to endothelial cells, which is a critical step in the migration of leukocytes to sites of inflammation. It does this by binding to its ligands, fibronectin and VCAM-1, which are expressed on the surface of endothelial cells.

In addition to its role in leukocyte migration, VLA-4 is also involved in other immune processes. For example, it plays a role in the formation of immune synapses, which are specialized contact areas between T cells and antigen-presenting cells.

Clinical significance

Given its crucial role in leukocyte migration, VLA-4 is a potential target for the treatment of inflammatory diseases. In fact, several drugs that inhibit VLA-4 have been developed and are currently in clinical use or under investigation. These include natalizumab, a monoclonal antibody that blocks VLA-4 and is used in the treatment of multiple sclerosis and Crohn's disease.

See also

• Integrin
• Leukocyte
• Fibronectin
• VCAM-1
• T cell
• Immune synapse
• Natalizumab

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