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