Intercellular adhesion molecule 1 (ICAM-1) – Lymphocyte function-associated antigen 1 (LFA-1) complex (ICAM-1 – LFA-1 complex)

The ICAM-1 – LFA-1 complex is a critical molecular interaction between Intercellular Adhesion Molecule 1 (ICAM-1, CD54), expressed on endothelial cells and antigen-presenting cells, and Lymphocyte Function-associated Antigen 1 (LFA-1, integrin αLβ2), expressed on the surface of leukocytes (UniProt P05362, P20333). This interaction facilitates the firm adhesion of lymphocytes to the vascular endothelium, which is a prerequisite for leukocyte extravasation into inflamed tissues (PubMed: 15103330). Beyond structural adhesion, the complex serves as a potent costimulatory signal for T-cell activation and the formation of the immunological synapse. Dysregulation of this pathway is central to the pathogenesis of various inflammatory and autoimmune disorders, including dry eye disease and psoriasis. Therapeutic strategies, such as the small molecule lifitegrast, involve competitive inhibition of the binding of LFA-1 to ICAM-1, thereby reducing inflammatory cell infiltration and cytokine release (FDA Label, Lifitegrast). Historically, monoclonal antibodies like efalizumab also targeted this complex, though safety concerns such as PML led to their withdrawal from certain markets.

Other names

CD54-CD11a/CD18 complexICAM-1/LFA-1 interactionIntegrin alpha-L beta-2 – ICAM-1 complexLeukocyte adhesion complex

Competitive inhibition of the LFA-1/ICAM-1 interaction to block leukocyte recruitment and T-cell activation.