Identification and characterization of DC-SIGN-binding glycoproteins in allergenic foods.
BACKGROUND
DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) is a C-type lectin receptor expressed on macrophages and dendritic cells. DC-SIGN has high affinity for fucosylated glycans in several plant glycoproteins and pathogens. DC-SIGN is thought to be crucial for the development of allergic sensitization. However, the precise role of DC-SIGN in food allergy pathogenesis is not yet understood.


OBJECTIVE
We sought to characterize DC-SIGN-binding glycoproteins in a panel of allergenic and non-allergenic foods.


METHODS
Fluorescent-labeled peanut and soy extracts were used to test protein binding to human monocyte-derived dendritic cells (DCs) by flow cytometry. DC-SIGN-blocking assays were performed by incubating DCs with food extracts followed by staining with anti-DC-SIGN antibody. Using a DC-SIGN-Fc chimera, food extracts were tested for binding by ELISA and autoradiography. IgE immunoblotting was performed with pooled sera from food-allergic subjects. DC activation and maturation were assessed by flow cytometry.


RESULTS AND CONCLUSIONS
We demonstrate that peanut agglutinin, a minor peanut allergen, is a novel ligand for DC-SIGN. Peanut agglutinin activates DCs to induce the expression of costimulatory molecules in vitro. We present a comprehensive report on the characterization of DC-SIGN-binding proteins in common allergenic foods such as peanut, soy, tree nuts, egg, and milk. Foods that rarely induce allergy, such as pine nuts, chickpea, and corn, showed no binding to DC-SIGN. Several DC-SIGN-binding proteins show reactivity in serum IgE immunoblots. We have also identified novel non-IgE-binding proteins that interact with DC-SIGN; these proteins may be important for regulating immune responses to these foods.
['Kamalakannan|M|M|', 'Chang|L M|LM|', 'Grishina|G|G|', 'Sampson|H A|HA|', 'Masilamani|M|M|']
D000485:Allergens D015415:Biomarkers D002352:Carrier Proteins D015815:Cell Adhesion Molecules D003429:Cross Reactions D003713:Dendritic Cells D004797:Enzyme-Linked Immunosorbent Assay D005434:Flow Cytometry D005502:Food D005504:Food Analysis D005512:Food Hypersensitivity D006023:Glycoproteins D006801:Humans D007073:Immunoglobulin E D037181:Lectins, C-Type D008024:Ligands D010940:Plant Proteins D011485:Protein Binding D011956:Receptors, Cell Surface
DC-SIGN peanut peanut agglutinin food allergens soybean