Integrin alpha E beta 7, also called HML-1 (human mucosal lymphocyte antigen), is the only known integrin family adhesion receptor containing the alpha E (epithelial-associated) subunit, and shares the beta 7 subunit with alpha 4 beta 7 (1-3). alpha E beta 7 is the non‑covalent multimer of alpha E (designated CD103), present as 150 kDa and 25 kDa heavy and light chains, and 130 kDa beta 7 type I transmembrane glycoprotein subunits (2, 3). The alpha E extracellular N-terminal beta -propeller structure contains X (which contains the cleavage site) and I domains, and is followed by domains called thigh, calf-1 and calf-2 (1, 2). The beta 7 ECD contains a vWFA domain, which interacts with the alpha E beta ‑propeller to form a binding domain. The MIDAS motif (metal ion‑dependent adhesion site) is critical for binding of alpha E beta 7 to its ligand (4). Each subunit has a transmembrane sequence and a short cytoplasmic tail. The 1105 aa human alpha E extracellular domain shares 70-79% aa sequence identity with mouse, rat, equine, bovine, canine and feline alpha E, while the 705 aa human beta 7 ECD shares 87%, 87%, 91% and 88% aa identity with mouse, rat, equine and bovine beta 7, respectively. alpha E beta 7 is mainly restricted to mucosal tissues, where it engages the epithelial adhesion molecule E-cadherin (4-6). It was first identified as a marker of intestinal intra-epithelial lymphocytes (2, 5, 6). It has since been recognized that a variety of leukocytes, such as cytotoxic CD8+ T cells, some dendritic cells, and effector/memory-like regulatory T cells, acquire alpha E beta 7 in the days following their migration to epithelial tissues such as the intestines, lungs, and epithelial layers of tonsils (6-13). In these tissues alpha E beta 7 facilitates immune surveillance, including destruction of infected or transformed epithelial cells and induction of T cell adaptive responses (7-13). Pathologically, alpha E beta 7 may be involved in allograft rejection of transplanted pancreatic islets and other tissues (14).