Human T-lymphocyte activation is associated with changes in O-glycan biosynthesis.

F Piller,V Piller,R I Fox,M Fukuda

doi:10.1016/s0021-9258(18)68157-8

Abstract

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.

Highlights

THEJOURNALOF BIOLOGICACLHEMISTRY0 1988 by The American Society for Biochemistry and Molecular Biology, Inc. Val. 263, No 29, Issue of October 15, pp. 1514615150,1988 Printed in U.S.A
The activation of human T-lymphocytes by anti-CD3 PAGE’ depends largely on thestructures of the0-linked antibodies and interleukin-2 results in a marked in- glycans and the extent of sialylation [14]
NAc-Ser/Thr, whereas activated human T-cells carry protein carries a large portion of the cell-surface carbohyon leukosialin exclusively themore complex structures drates of T-lymphocytes, and the comparison of its glycan

Summary

THEJOURNALOF BIOLOGICACLHEMISTRY

0 1988 by The American Society for Biochemistry and Molecular Biology, Inc. Val. 263, No 29, Issue of October 15, pp. 1514615150,1988 Printed in U.S.A. The activation of human T-lymphocytes by anti-CD3 PAGE’ depends largely on thestructures of the0-linked antibodies and interleukin-2 results in a marked in- glycans and the extent of sialylation [14] This glycoprotein crease in apparent molecular weight of the major cell- is present on all human leukocytes and has been called leusurface sialoglycoprotein. All assays followed the optimized published procedures, and the concentration and the specific radioactivity for the sugar nucleotides were usually 0.1 mM and 100,000 cpm/nmol, respectively, except for the a2-6 sialyltransferase (0.5 mM and 20,000 showed (Fig. 1B)that this antiserum recognizes the major glycoprotein on resting as well as activated human T-lymphocytes. In order to test thehypothesis that different carbohydrate structures are present on leukosialin from resting and activated human T-lymphocytes, the cells were labeled in their sugarportions, either on the cell surface (resting cells) or

AND DISCUSSION

Fraction Number

Enzyme activities