Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase

Cell. 2001 Jun 29;105(7):957-69. doi: 10.1016/s0092-8674(01)00394-4.

Abstract

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 beta 1-->4(sulfo-->6)GlcNAc beta 1-->3Gal beta 1-->3GalNAc, as the MECA-79 epitope. Molecular cloning of a HEV-expressed core1-beta 1,3-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / chemistry
  • Antigens, Surface / metabolism*
  • CHO Cells
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cell Adhesion / physiology
  • Cricetinae
  • Epitopes / chemistry
  • Epitopes / metabolism
  • Humans
  • Immunoblotting
  • In Situ Hybridization
  • L-Selectin / metabolism
  • Ligands
  • Lymphoid Tissue / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / metabolism*
  • Polysaccharides / biosynthesis
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Receptors, Lymphocyte Homing / chemistry
  • Receptors, Lymphocyte Homing / metabolism*
  • Sulfates / metabolism
  • Transfection
  • Venules / chemistry
  • Venules / metabolism

Substances

  • Antigens, Surface
  • Epitopes
  • L-selectin counter-receptors
  • Ligands
  • Membrane Proteins
  • Polysaccharides
  • Receptors, Lymphocyte Homing
  • Sulfates
  • L-Selectin
  • N-Acetylglucosaminyltransferases

Associated data

  • GENBANK/AF149783
  • GENBANK/AF293973