title: Human T cell activation results in extracellular signal-regulated kinase (ERK)-calcineurin-dependent exposure of Tn antigen on the cell surface and binding of the macrophage galactose-type lectin (MGL).
abstract: The C-type lectin macrophage galactose-type lectin (MGL) exerts an immunosuppressive role reflected by its interaction with terminal GalNAc moieties, such as the Tn antigen, on CD45 of effector T cells, thereby down-regulating T cell receptor signaling, cytokine responses, and induction of T cell death. Here, we provide evidence for the pathways that control the specific expression of GalNAc moieties on human CD4(+) T cells. GalNAc epitopes were readily detectable on the cell surface after T cell activation and required de novo protein synthesis. Expression of GalNAc-containing MGL ligands was completely dependent on PKC and did not involve NF-κB. Instead, activation of the downstream ERK MAPK pathway led to decreased mRNA levels and activity of the core 1 β3GalT enzyme and its chaperone Cosmc, favoring the expression of Tn antigen. In conclusion, expression of GalNAc moieties mirrors the T cell activation status, and thus only highly stimulated T cells are prone to the suppressive action of MGL.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands. Electronic address: s.vanvliet@vumc.nl.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Ilona M
authors.initials: IM
authors.lastname: Vuist
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Lenos
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Boris
authors.initials: B
authors.lastname: Tefsen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: García-Vallejo
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019703:Calcineurin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005700:Galactosyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D005964:Glucosyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C505369:C1GALT1C1 protein, human; D037181:Lectins, C-Type; C506225:MGL lectin, human; D018832:Molecular Chaperones; C040286:Tn antigen; C514116:B3GLCT protein, human; D005700:Galactosyltransferases; D005964:Glucosyltransferases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019703:Calcineurin; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: C-type Lectin; ERK; Glycosylation; Lectin; Signaling; T Cell
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