Leukocyte function-associated antigen 1 (LFA-1)

Leukocyte function-associated antigen 1 (LFA-1) is a heterodimeric integrin found on lymphocytes and other leukocytes. It is composed of an alpha subunit (αL, CD11a) and a beta subunit (β2, CD18). LFA-1 exists in multiple conformational states (low, intermediate, and high affinity) and its activation via 'inside-out signaling' (often triggered by chemokines) leads to a transition to the high-affinity state, exposing the MIDAS binding site within the alpha subunit's I-domain. This site requires divalent cations (Mg2+, Mn2+) for ligand binding. Key ligands include ICAM-1, ICAM-2, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1 plays crucial roles in immune cell function, including leukocyte adhesion and migration, immunological synapse formation, cytotoxic T cell function, immune cell activation, and cytotoxic killing. Due to its central role in immune and inflammatory processes, LFA-1 is a therapeutic target for conditions such as inflammatory diseases, autoimmune disorders, cardiovascular diseases, and cancer metastasis. Inhibitors targeting the LFA-1 I domain have been developed.

Other names

CD11a/CD18

Blocking LFA-1-ligand interactions, particularly LFA-1/ICAM-1 interactions, often by targeting the LFA-1 I domain, to inhibit leukocyte adhesion, migration, and subsequent immune processes.