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 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.
Yeh
J C
JC
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Hiraoka
N
N
Petryniak
B
B
Nakayama
J
J
Ellies
L G
LG
Rabuka
D
D
Hindsgaul
O
O
Marth
J D
JD
Lowe
J B
JB
Fukuda
M
M
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism*; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000502:physiology; D006224:Cricetinae; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D019041:L-Selectin / Q000378:metabolism; D008024:Ligands; D008221:Lymphoid Tissue / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D014162:Transfection; D014699:Venules / Q000737:chemistry / Q000378:metabolism
D000954:Antigens, Surface; D000939:Epitopes; C069886:L-selectin counter-receptors; D008024:Ligands; D008565:Membrane Proteins; D011134:Polysaccharides; D016201:Receptors, Lymphocyte Homing; D013431:Sulfates; D019041:L-Selectin; D017351:N-Acetylglucosaminyltransferases