VLA-4

Integrin alpha4beta1 (Very Late Antigen-4) is an integrin dimer. It is composed of CD49d (alpha 4) and CD29 (beta 1).

Vascular cell adhesion molecule-1 (VCAM-1 - an integrin receptor) located on an endothelial cell, binds to the integrin VLA-4 which are normally expressed on leukocyte plasma membranes, but they do not adhere to their appropriate ligands until the leukocytes are activated by chemotactic agents or other stimuli (often produced by the endothelium or other cells at the site of injury). Only then do the integrins undergo the conformational change necessary to confer high binding affinity for the endothelial adhesion molecules.

In multiple sclerosis, the VLA-4 integrin is essential in the processes by which T-cells gain access to the brain by allowing the cells to penetrate the blood brain barrier that normally restricts immune cell access. One approach to prevent an autoimmune reaction has been to block the action of VLA-4 so that self-reactive T-cells are unable to enter the brain and thus unable to attack myelin protein.