Lymphocyte adhesion to epithelia and endothelia mediated by the lymphocyteendothelial-epithelial cell adhesion molecule (LEEP-CAM) glycoprotein

Upon encountering the relevant vascular bed, lymphocytes attach to endothel ial adhesion molecules, transmigrate out of circulation, and localize withi n tissues. Lymphocytes may then be retained at microanatomic sites, as in t issues, or they may continue to migrate to the lymphatics and recirculate i n the blood. Lymphocytes also interact transiently, but with high avidity, with target cells or APC that are infected with microbes or hare taken up e xogenous foreign Ags, This array of adhesive capabilities is mediated by th e selective expression of lymphocyte adhesion molecules. Here, we developed the 6F10 mAb, which recognizes a cell surface glycoprotein designated lymp hocyte endothelial-epithelial cell adhesion molecule (LEEP-CAM), that is di stinct in biochemical characteristics and distribution of expression from o ther molecules known to play a role in lymphocyte adhesion. LEEP-CAM is exp ressed on particular epithelia, including the suprabasal region of the epid ermis, the basal layer of bronchial and breast epithelia, and throughout th e tonsillar and vaginal epithelia, Yet, it is absent from intestinal and re nal epithelia, Interestingly, it is expressed also on vascular endothelium, especially high endothelial venules (HEV) in lymphoid organs, such as tons il and appendix, The anti-LEEP-CAM: mAb specifically blocked T and B lympho cyte adhesion to monolayers of epithelial cells and to vascular endothelial cells in static cell-to-cell binding assays by similar to 40-60% when comp ared with control mAbs, These data suggest a role for this newly identified molecule in lymphocyte binding to endothelium, as well as adhesive interac tions within selected epithelia.