Recombinant Human Integrin alpha L beta 2 Protein, CF

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 (5, 6). 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, 6-9). Active alpha L beta 2 binds ICAM-1/CD54, ICAM-2, ICAM‑3 and JAM‑A (1, 10-12). The adhesion stabilizes interactions between T cells and antigen-presenting cells, decreases the T cell activation threshold, and facilitates leukocyte transendothelial migration to sites of inflammation (12-14). A constitutively active construct severely impairs immune responses, demonstrating that both activation and de-activation are important (14). Mutations of beta 2, especially in the vWFA domain, cause leukocyte adhesion deficiency (LAD-1) and susceptibility to bacterial infections (15). The 1088 amino acid (aa) human alpha L/CD11b ECD is 73-74% aa identical to mouse and rat, and 79-80% aa identical to bovine, porcine, ovine, goat and canine  alpha L ECD. A second human alpha L isoform has 53 aa inserted after aa 954 in the ECD. The 678 aa human beta 2/CD18 ECD shares 81-83% aa sequence identity with mouse, rat, bovine, canine, goat, ovine, and porcine beta 2 ECD.