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)

J Biol Chem. 2013 Sep 20;288(38):27519-27532. doi: 10.1074/jbc.M113.471045. Epub 2013 Aug 5.

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.

Keywords: C-type Lectin; ERK; Glycosylation; Lectin; Signaling; T Cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / genetics
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Calcineurin / genetics
  • Calcineurin / immunology*
  • Calcineurin / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / immunology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Galactosyltransferases / biosynthesis
  • Galactosyltransferases / genetics
  • Galactosyltransferases / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Glucosyltransferases / biosynthesis
  • Glucosyltransferases / genetics
  • Glucosyltransferases / immunology
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation / physiology*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology*
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / genetics
  • Molecular Chaperones / immunology
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology
  • Protein Kinase C / metabolism

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • C1GALT1C1 protein, human
  • Lectins, C-Type
  • MGL lectin, human
  • Molecular Chaperones
  • Tn antigen
  • B3GLCT protein, human
  • Galactosyltransferases
  • Glucosyltransferases
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
  • Calcineurin
  • Leukocyte Common Antigens
  • PTPRC protein, human