Lymphocyte function-associated antigen-1 and Very late antigen-4 (LFA-1 and VLA-4)

Lymphocyte function-associated antigen-1 (LFA-1, integrin alpha-L beta-2) and Very late antigen-4 (VLA-4, integrin alpha-4 beta-1) are heterodimeric transmembrane receptors expressed on the surface of T cells and other leukocytes [UniProt P20333, P13612]. They belong to the integrin family of cell adhesion molecules and play pivotal roles in the immune response by mediating leukocyte-endothelial cell adhesion and migration into inflamed tissues [PubMed: 17110315]. LFA-1 primarily interacts with Intercellular Adhesion Molecule-1 (ICAM-1), while VLA-4 binds to Vascular Cell Adhesion Molecule-1 (VCAM-1) and fibronectin [StatPearls: Integrins]. These interactions are critical for the recruitment of T cells to sites of inflammation and the formation of the immunological synapse during antigen presentation [PubMed: 12496951]. In autoimmune and inflammatory diseases, such as multiple sclerosis and dry eye disease, these integrins are overactive, leading to excessive tissue infiltration by immune cells [PubMed: 15951574]. Therapeutic strategies involve monoclonal antibodies or small molecules that block these receptors to prevent leukocyte extravasation, such as Natalizumab for multiple sclerosis and Lifitegrast for dry eye disease [FDA: Tysabri, Xiidra]. However, such interventions carry significant safety concerns, most notably the risk of progressive multifocal leukoencephalopathy (PML) due to impaired immune surveillance in the central nervous system [NEJM: 15951574].

Other names

CD11a/CD18 and CD49d/CD29Integrin alpha-L beta-2 and Integrin alpha-4 beta-1Leukocyte integrinsLFA-1 and VLA-4

Antagonism of integrin-ligand interactions (e.g., LFA-1/ICAM-1 and VLA-4/VCAM-1) to inhibit leukocyte recruitment and activation.