TY - JOUR
T1 - Surface expression of transglutaminase 2 by dendritic cells and its potential role for uptake and presentation of gluten peptides to T cells
AU - Ráki, M.
AU - Schjetne, K. W.
AU - Stamnaes, J.
AU - Molberg,
AU - Jahnsen, F. L.
AU - Issekutz, T. B.
AU - Bogen, B.
AU - Sollid, L. M.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1365-3083.2006.01881.x
DO - 10.1111/j.1365-3083.2006.01881.x
M3 - Article
C2 - 17309775
AN - SCOPUS:33847033626
SN - 0300-9475
VL - 65
SP - 213
EP - 220
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
IS - 3
ER -