Human T-lymphocyte activation is associated with changes in O-glycan biosynthesis.
The activation of human T-lymphocytes by anti-CD3 antibodies and interleukin-2 results in a marked increase in apparent molecular weight of the major cell-surface sialoglycoprotein. Both forms of the sialoglycoprotein were identified as leukosialin by a monospecific antiserum, and the differences in molecular weight were found to be due to changes in the carbohydrate structures. Our results suggest that resting T-lymphocytes express on leukosialin the disialotetrasaccharides NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----6)Gal-NAc-Ser/Thr, whereas activated human T-cells carry on leukosialin exclusively the more complex structures NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6)GalNAc-Ser/Thr. The radical shift in the biosynthetic pathway of O-glycans in activated T-lymphocytes compared to resting cells is apparently caused by a decrease of alpha 2----6 sialyltransferase activity and by the parallel dramatic stimulation of the beta 1----6GlcNAc-transferase. Since both enzymes compete for the same precursor substrate, the coordinate changes in their activities are most likely responsible for the complete change of the carbohydrate structures on leukosialin during the activation of human T-lymphocytes.
Piller
F
F
Cancer Research Center, La Jolla Cancer Research Foundation, California.
Piller
V
V
Fox
R I
RI
Fukuda
M
M
D015703:Antigens, CD; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006801:Humans; D007106:Immune Sera; D066298:In Vitro Techniques; D051917:Leukosialin; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000302:isolation & purification; D011134:Polysaccharides / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D007106:Immune Sera; D051917:Leukosialin; D009844:Oligosaccharides; D011134:Polysaccharides; C465014:SPN protein, human; D012795:Sialoglycoproteins