Surface expression of transglutaminase 2 by dendritic cells and its potential role for uptake and presentation of gluten peptides to T cells.
Celiac disease is a chronic small intestinal inflammation driven by gluten-reactive T cells of the intestinal mucosa. These T cells are HLA-DQ2 or -DQ8 restricted, and predominantly recognize gluten peptides that are deamidated by the enzyme transglutaminase 2 (TG2). Our recent results strongly suggest that duodenal CD11c(+) dendritic cells (DC) are directly involved in T cell activation in the celiac lesion. The aim of this study was to investigate whether surface-associated TG2 could be involved in receptor-mediated endocytosis of gluten peptides, a process that may contribute to the preferential recognition of deamidated peptides. We found that both monocyte-derived DC and local CD11c(+) DC in the duodenal mucosa expressed cell surface-associated TG2. As phenotypic characterization of CD11c(+) DC in the celiac lesion suggests that these cells may be derived from circulating monocytes, we used monocyte-derived DC in functional in vitro studies. Using a functional T cell assay, we obtained evidence that cell surface-associated TG2 is endocytosed by monocyte-derived DC. However, we were unable to obtain evidence for a role of surface TG2 in the loading and subsequent generation of deamidated gluten peptides in these cells.
Ráki
M
M
Institute of Immunology, The Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway. melinda.raki@medisin.uio.no
Schjetne
K W
KW
Stamnaes
J
J
Molberg
Ø
Ø
Jahnsen
F L
FL
Issekutz
T B
TB
Bogen
B
B
Sollid
L M
LM
D017951:Antigen Presentation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D005983:Glutens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013601:T-Lymphocytes / Q000276:immunology*; D011503:Transglutaminases / Q000096:biosynthesis*
D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins