Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GIcNAc-6-sulf ate as an essential posttranslational modification for ligand activity. Her e, we show that genetic deletion of HEC-GIcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombin ant L-selectin to the luminal aspect of HEV, elimination of lymphocyte bind ing in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chr onic inflammatory sites, is also lost from the luminal aspects of HEV. Thes e results establish a critical role for HEC-GIcNAc6ST in lymphocyte traffic king and suggest it as an important therapeutic target.