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

The Intercellular adhesion molecule 1 – Lymphocyte function-associated antigen 1 (ICAM-1 – LFA-1) interface is a pivotal protein-protein interaction that mediates leukocyte-endothelial cell adhesion and costimulation. ICAM-1 (CD54) is a member of the immunoglobulin superfamily expressed on endothelial cells and antigen-presenting cells, while LFA-1 (integrin αLβ2) is expressed on the surface of all leukocytes (UniProt P05362, P20333). The binding of LFA-1 to ICAM-1 is essential for the arrest of rolling leukocytes on the vascular wall and their subsequent transendothelial migration into tissues during an immune response (PubMed: 10880524). Furthermore, this interaction provides a critical costimulatory signal that stabilizes the immunological synapse between T-cells and antigen-presenting cells, facilitating robust T-cell activation and proliferation (PubMed: 15507514). Dysregulation of the ICAM-1 – LFA-1 interface is a hallmark of various inflammatory and autoimmune disorders, including dry eye disease, psoriasis, and rheumatoid arthritis (StatPearls: NBK539824). Therapeutic agents like lifitegrast target this interface by binding to the I-domain of LFA-1, thereby blocking its interaction with ICAM-1 and reducing the recruitment and activation of T-lymphocytes (PubChem CID: 11557544). While effective, targeting this pathway can lead to safety concerns such as localized irritation or, in the case of systemic biologics like efalizumab, an increased risk of serious infections and progressive multifocal leukoencephalopathy (FDA).

Other names

ICAM-1/LFA-1 interactionCD54-CD11a/CD18 interfaceIntegrin alpha-L beta-2/ICAM-1 complexLeukocyte adhesion interface

Competitive inhibition of the LFA-1 I-domain to prevent ICAM-1 binding, blockade of leukocyte adhesion, and inhibition of T-cell costimulation (PubChem CID: 11557544, PubMed: 10880524)