Lymphocyte function-associated antigen 1 (LFA-1) (LFA-1)

Lymphocyte function-associated antigen 1 (LFA-1) is a heterodimeric integrin composed of the alpha L (CD11a) and beta 2 (CD18) subunits, expressed on the surface of all leukocytes, particularly lymphocytes [1, 16]. It is a key mediator of the immune response, facilitating the firm adhesion of leukocytes to the vascular endothelium and their subsequent transmigration into tissues by binding to ligands such as Intercellular Adhesion Molecule-1 (ICAM-1) [6, 16]. Beyond trafficking, LFA-1 is essential for the formation of the immunological synapse between T cells and antigen-presenting cells, providing costimulatory signals necessary for T-cell activation and proliferation [12, 17]. Dysfunctional LFA-1 expression or activity is linked to various pathologies; for instance, its absence causes Leukocyte Adhesion Deficiency type I (LAD-I), while its overactivity contributes to chronic inflammatory diseases like psoriasis and dry eye disease [1, 17]. Pharmacological targeting of LFA-1, through agents like the small molecule lifitegrast or the monoclonal antibody efalizumab, aims to disrupt the LFA-1/ICAM-1 axis to alleviate inflammation [1, 10]. However, systemic inhibition has been associated with serious risks such as progressive multifocal leukoencephalopathy, leading to the withdrawal of some therapies [10].

Other names

CD11a/CD18Integrin alpha-L/beta-2ITGAL/ITGB2Lymphocyte function-associated antigen 1LFA-1

LFA-1 antagonist; inhibits the interaction between LFA-1 and its ligand ICAM-1, thereby blocking T-cell activation, adhesion, and migration into inflamed tissues.