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

The Lymphocyte function-associated antigen-1 (LFA-1) – Intercellular adhesion molecule-1 (ICAM-1) interface is a critical protein-protein interaction involved in the recruitment and activation of leukocytes during the immune response (UniProt P20333, P05362). LFA-1, an integrin expressed on the surface of T-cells, binds to ICAM-1 on endothelial cells to facilitate firm adhesion and transmigration into tissues (PubMed: 10623514). This interaction is essential for the formation of the immunological synapse and the subsequent release of inflammatory cytokines (PubMed: 11739552). Dysregulation of this pathway is a hallmark of various inflammatory and autoimmune conditions, including dry eye disease and psoriasis (StatPearls: NBK539824). Therapeutic strategies targeting this interface, such as the small molecule lifitegrast, aim to block the binding of LFA-1 to ICAM-1, thereby reducing T-cell mediated inflammation (PubChem CID: 11647372). While effective, systemic inhibition of this pathway has historically been associated with risks of immunosuppression, leading to a preference for localized delivery in certain indications (FDA: Efalizumab safety).

Other names

LFA-1/ICAM-1 interactionIntegrin alpha-L beta-2 – CD54 interfaceCD11a/CD18 – Intercellular adhesion molecule-1 complexITGAL/ITGB2 – ICAM1 interface

Antagonism of the LFA-1/ICAM-1 interaction, either through competitive binding to the LFA-1 I-domain or allosteric modulation, which prevents leukocyte adhesion, migration, and T-cell activation (PubMed: 17114019).