Integrin alpha L beta 2, also called LFA-1, is one of three beta 2 integrin adhesion proteins. The non‑covalent heterodimer of 180 kDa alpha L/CD11a and 95 kDa beta 2/CD18 integrin subunits is expressed on virtually all leukocytes (1‑3). The ligand binding site of LFA-1 is in the N-terminal head region, formed by an interaction of the vWFA
(I, I‑like) domains from each subunit, and the alpha L beta-propeller structure (3‑5). The alpha L subunit contains domains termed thigh, calf-1 and calf-2, while the beta 2 subunit contains a PSI (plexin-semaphorin-integrin) region and four cysteine-rich I-EGF folds (3). Each subunit has a transmembrane sequence and a short cytoplasmic tail connected to the cytoskeleton. Upon activation by “inside‑out” signaling, clustering, or Mg²⁺ or Mn²⁺ binding to metal ion-dependent adhesion sites (MIDAS) within the vWFA domains, the molecule unfolds from its inactive, “closed” conformation to expose ligand binding sites (3‑7). Active alpha L beta 2 binds ICAM-1/CD54, ICAM-2, ICAM-3 and JAM-A (1, 8‑10). The adhesion stabilizes interactions between T cells and antigen-presenting cells, decreases the T cell activation threshold, and facilitates transendothelial migration of neutrophils and other leukocytes to sites of inflammation (10‑13). Blockade of LFA-1 may inhibit graft vs. host disease and transplant rejection (14). A constitutively active construct severely impairs immune responses, demonstrating that both activation and de-activation are important (12). Mutations of beta 2, especially in the vWFA domain, cause leukocyte adhesion deficiency (LAD-1) and susceptibility to bacterial infections (15). The 1065 amino acid (aa) mouse alpha L/CD11b ECD shares 87% aa sequence identity with rat, and 70‑74% with human, equine, bovine, porcine, and canine  alpha L ECD. Potential mouse alpha L isoforms of 626 and 601 aa have alternate N- or C-termini, respectively. The 679 aa mouse beta 2/CD18 ECD shares 91% aa sequence identity with rat, and 80-82% with human, bovine, canine, and porcine beta 2 ECD.