An alternate core 2 beta1,6-N-acetylglucosaminyltransferase selectively contributes to P-selectin ligand formation in activated CD8 T cells.
Core 2 beta1,6-N-acetylglucosaminyltransferase (C2GlcNAcT) synthesizes essential core 2 O-glycans on selectin ligands, which mediate cell-cell adhesion required for lymphocyte trafficking. Although gene-deletion studies have implicated C2GlcNAcT-I in controlling selectin ligand-mediated cell trafficking, little is known about the role of the two other core 2 isoenzymes, C2GlcNAcT-II and C2GlcNAcT-III. We show that C2GlcNAcT-I-independent P-selectin ligand formation occurs in activated C2GlcNAcT-I(null) CD8 T cells. These CD8 T cells were capable of rolling under shear flow on immobilized P-selectin in a P-selectin glycoprotein ligand 1-dependent manner. RT-PCR analysis identified significant levels of C2GlcNAcT-III RNA, identifying this enzyme as a possible source of core 2 enzyme activity. Up-regulation of P-selectin ligand correlated with altered cell surface binding of the core 2-sensitive mAb 1B11, indicating that CD43 and CD45 are also physiological targets for this alternate C2GlcNAcT enzyme. Furthermore, C2GlcNAcT-I-independent P-selectin ligand induction was observed in an in vivo model. HY(tg) CD8 T cells from C2GlcNAcT-I(null) donors transferred into male recipients expressed P-selectin ligand in response to male Ag, although at reduced levels compared with wild-type HY(tg) CD8 T cells. Our data demonstrate that multiple C2GlcNAcT enzymes can contribute to P-selectin ligand formation and may cooperate with C2GlcNAcT-I in the control of CD8 T cell trafficking.
Merzaban
Jasmeen S
JS
Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Zuccolo
Jonathan
J
Corbel
Stéphane Y
SY
Williams
Michael J
MJ
Ziltener
Hermann J
HJ
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006182:H-Y Antigen / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D036904:Leukocyte Rolling; D051917:Leukosialin; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D012313:RNA / Q000032:analysis; D012795:Sialoglycoproteins / Q000378:metabolism
D015703:Antigens, CD; D006182:H-Y Antigen; D051917:Leukosialin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D012313:RNA; D017351:N-Acetylglucosaminyltransferases; D017493:Leukocyte Common Antigens