Abstract
We analyzed the autologous NK cell interaction with gliadin-presenting dendritic cells. Gliadin is the known Ag priming the celiac disease (CD) pathogenesis. We demonstrate that gliadin prevents immature dendritic cells (iDCs) elimination by NK cells. Furthermore, cooperation between human NK cells-iDCs and T cells increases IFN-gamma production of anti-gliadin immune response. Gliadin fractions were analyzed for their capability to stabilize HLA-E molecules. The alpha and omega fractions conferred the protection from NK cell lysis to iDCs and increased their HLA-E expression. Gliadin pancreatic enzyme digest and a peptide derived from gliadin alpha increased HLA-E levels on murine RMA-S/HLA-E-transfected cells. Analysis of HLA-E expression in the small intestinal mucosa of gluten-containing diet celiac patients and organ culture experiments confirmed the in vitro data.
MeSH terms
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Adolescent
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Adult
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Communication / drug effects
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Cell Communication / immunology*
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Cell Differentiation / immunology
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / immunology
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Cell Membrane / metabolism*
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Child
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Cytotoxicity, Immunologic / drug effects
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Female
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Gliadin / pharmacology*
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HLA Antigens / biosynthesis
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HLA Antigens / metabolism*
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HLA-E Antigens
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Immunophenotyping
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Intestinal Mucosa / cytology
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / immunology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Lactoglobulins / physiology
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Male
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Mice
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Organ Culture Techniques
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Peptides / physiology
Substances
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Epitopes, T-Lymphocyte
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HLA Antigens
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Histocompatibility Antigens Class I
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Lactoglobulins
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Peptides
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Gliadin