title: An investigation into IgE-facilitated allergen recognition and presentation by human dendritic cells.
abstract: BACKGROUND
  Allergen recognition by dendritic cells (DCs) is a key event in the allergic cascade leading to production of IgE antibodies. C-type lectins, such as the mannose receptor and DC-SIGN, were recently shown to play an important role in the uptake of the house dust mite glycoallergen Der p 1 by DCs. In addition to mannose receptor (MR) and DC-SIGN the high and low affinity IgE receptors, namely FcεRI and FcεRII (CD23), respectively, have been shown to be involved in allergen uptake and presentation by DCs.
  
  
  OBJECTIVE
  This study aims at understanding the extent to which IgE- and IgG-facilitated Der p 1 uptake by DCs influence T cell polarisation and in particular potential bias in favour of Th2. We have addressed this issue by using two chimaeric monoclonal antibodies produced in our laboratory and directed against a previously defined epitope on Der p 1, namely human IgE 2C7 and IgG1 2C7.
  
  
  RESULTS
  Flow cytometry was used to establish the expression patterns of IgE (FcεRI and FcεRII) and IgG (FcγRI) receptors in relation to MR on DCs. The impact of FcεRI, FcεRII, FcγRI and mannose receptor mediated allergen uptake on Th1/Th2 cell differentiation was investigated using DC/T cell co-culture experiments. Myeloid DCs showed high levels of FcεRI and FcγRI expression, but low levels of CD23 and MR, and this has therefore enabled us to assess the role of IgE and IgG-facilitated allergen presentation in T cell polarisation with minimal interference by CD23 and MR. Our data demonstrate that DCs that have taken up Der p 1 via surface IgE support a Th2 response. However, no such effect was demonstrable via surface IgG.
  
  
  CONCLUSIONS
  IgE bound to its high affinity receptor plays an important role in Der p 1 uptake and processing by peripheral blood DCs and in Th2 polarisation of T cells.
authors: Inas K
authors: IK
authors: Sharquie
authors: Abeer
authors: A
authors: Al-Ghouleh
authors: Patricia
authors: P
authors: Fitton
authors: Mike R
authors: MR
authors: Clark
authors: Kathryn L
authors: KL
authors: Armour
authors: Herb F
authors: HF
authors: Sewell
authors: Farouk
authors: F
authors: Shakib
authors: Faculty of Medicine and Health Sciences, Division of Immunology, University of Nottingham, Queen's Medical Centre, Nottingham, UK. amir.ghaemmaghami@nottingham.ac.uk.
authors: Amir M
authors: AM
authors: Ghaemmaghami
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology*; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000378:metabolism; D060829:Arthropod Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008351:Mannans / Q000276:immunology / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1