Journal
CELL
Volume 105, Issue 7, Pages 957-969Publisher
CELL PRESS
DOI: 10.1016/S0092-8674(01)00394-4
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Funding
- NCI NIH HHS [P01CA79132, F32CA79130, CA48737] Funding Source: Medline
- NIDDK NIH HHS [DK48247] Funding Source: Medline
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L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to addressins expressed in the high endothelial venules (HEV) of secondary lymphoid organs. Peripheral node addressin recognized by the MECA-79 antibody 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-glycan, Gal beta1-->4(sulfo-->6)GlcNAc beta1-->3Gal beta1--> 3GalNAc, as the MECA-79 epitope. Molecular cloning of a HEV-expressed core1-beta1,3-N-acetylglucosaminyltransferase (Core1-beta 3GlcNAcT) enabled the construction of the 6-sulfo sialyl Lewis x on extended core1 O-glycans, recapitulating the potent L-selectin-mediated, shear-dependent adhesion observed with novel L-selectin ligands derived from core2 beta1,6-N-acetylglucosaminyltransferase-I null mice. These results identify Core1-beta 3GlcNAcT and its cognate extended core1 O-glycans as essential participants in the expression of the MECA-79-positive, HEV-specific L-selectin ligands required for lymphocyte homing.
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