LFA-1 integrin

LFA-1 is a heterodimeric integrin composed of CD11a (αL subunit) and CD18 (β2 subunit), expressed on T cells, B cells, neutrophils, monocytes, and NK cells. During the leukocyte adhesion cascade, after selectin-mediated rolling and chemokine-induced activation, LFA-1 undergoes a conformational change (inside-out signaling) that increases its affinity for ICAM-1 (CD54) expressed on activated endothelium. This firm adhesion step (arrest) precedes diapedesis (transmigration) into inflamed tissue.

Beyond extravasation, LFA-1 plays a key role in the immunological synapse between T cells and antigen-presenting cells, stabilizing cell-cell contact and enhancing TCR signaling. It also contributes to cytotoxic T cell and NK cell killing by stabilizing conjugate formation with target cells.

Clinically, mutations in the CD18 gene cause Leukocyte Adhesion Deficiency type 1 (LAD-1), an autosomal recessive immunodeficiency. Patients present with recurrent bacterial infections without pus formation (impaired neutrophil migration), delayed umbilical cord separation, poor wound healing, and marked peripheral neutrophilia due to inability of neutrophils to leave the bloodstream. This is a classic USMLE topic distinguishing LAD-1 (CD18/integrin defect, impaired firm adhesion) from LAD-2 (defect in fucosylation affecting selectin ligands, impaired rolling).

LFA-1 is also a therapeutic target: efalizumab (an anti-LFA-1 monoclonal antibody) was previously used for psoriasis but withdrawn due to PML risk (JC virus reactivation), highlighting the importance of LFA-1 in normal immune surveillance.