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

The Lymphocyte function-associated antigen-1 (LFA-1) and Intercellular adhesion molecule 1 (ICAM-1) interface is a critical protein-protein interaction involved in the recruitment and activation of leukocytes (Source: UniProt P20333, P05362). LFA-1, an integrin expressed on the surface of T-cells, binds to ICAM-1 on endothelial cells or antigen-presenting cells to facilitate cell-to-cell adhesion and migration into inflamed tissues (Source: PubMed PMID: 17084201). This interaction is essential for the formation of the immunological synapse and the propagation of T-cell mediated immune responses. In pathological states, such as dry eye disease and psoriasis, overactivation of this pathway leads to chronic inflammation and tissue damage (Source: StatPearls, Dry Eye Disease). Drugs like lifitegrast target this interface by binding to the I-domain of LFA-1, thereby blocking its interaction with ICAM-1 and reducing the inflammatory response (Source: FDA Label, Xiidra). While effective, systemic inhibition of this interface has been associated with significant immunosuppressive risks, leading to the withdrawal of earlier agents like efalizumab, though topical applications remain a standard of care for localized inflammatory conditions (Source: PubMed PMID: 19641140).

Other names

CD11a/CD18–CD54 interactionIntegrin alpha-L beta-2–ICAM-1 interactionLFA-1–ICAM-1 adhesion complexITGAL/ITGB2–ICAM1 interface

Competitive inhibition of the protein-protein interaction between the I-domain of LFA-1 and the D1 domain of ICAM-1, preventing leukocyte recruitment and downstream inflammatory signaling.