A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34

L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion t o unique carbohydrate ligands, sulfated sialyl Lewis(x), which are expresse d on high endothelial venules (HEV) in secondary lymphoid organs. The natur e of the sulfotransferase(s) that contribute to sulfation of such L-selecti n counterreceptors has been uncertain. We herein describe a novel L-selecti n ligand sulfotransferase, termed LSST, that directs the synthesis of the 6 -sulfo sialyl Lewis(x) on L-selectin counterreceptors CD34, GlyCAM-1, and M AdCAM-1. LSST is predominantly expressed in HEV and exhibits striking catal ytic preference for core 2-branched mucin-type O-glycans as found in natura l L-selectin counterreceptors. LSST enhances L-selectin-mediated adhesion u nder shear compared to nonsulfated controls. LSST therefore corresponds to an HEV-specific sulfotransferase that contributes to the biosynthesis of L- selectin ligands required for lymphocyte homing.