Novel sulfated lymphocyte homing receptors and their control by a core1 extension beta 1,3-N-acetylglucosaminyltransferase

L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion t o addressins expressed in the high endothelial venules (HEV) of secondary l ymphoid organs. Peripheral node addressin recognized by the MECA-79 antibod y is apparently part of the L-selectin ligand, but its chemical nature has been undefined. We now identify a sulfated extended core1 mucin-type O-glyc an, Gal beta1-->4(sulfo-->6)GlcNAc beta1-->3Gal beta1--> 3GalNAc, as the ME CA-79 epitope. Molecular cloning of a HEV-expressed core1-beta1,3-N-acetylg lucosaminyltransferase (Core1-beta 3GlcNAcT) enabled the construction of th e 6-sulfo sialyl Lewis x on extended core1 O-glycans, recapitulating the po tent L-selectin-mediated, shear-dependent adhesion observed with novel L-se lectin ligands derived from core2 beta1,6-N-acetylglucosaminyltransferase-I null mice. These results identify Core1-beta 3GlcNAcT and its cognate exte nded core1 O-glycans as essential participants in the expression of the MEC A-79-positive, HEV-specific L-selectin ligands required for lymphocyte homi ng.