title: The minor house dust mite allergen Der p 13 is a fatty acid-binding protein and an activator of a TLR2-mediated innate immune response.
abstract: The house dust mite (HDM) allergen Der p 13 could be a lipid-binding protein able to activate key innate signaling pathways in the initiation of the allergic response. We investigated the IgE reactivity of recombinant Der p 13 (rDer p 13), its lipid-binding activities, and its capacity to stimulate airway epithelium cells.
  
  
  
  Purified rDer p 13 was characterized by mass spectrometry, circular dichroism, fluorescence-based lipid-binding assays, and in silico structural prediction. IgE-binding activity and allergenic potential of Der p 13 were examined by ELISA, basophil degranulation assays, and in vitro airway epithelial cell activation assays.
  
  
  
  Protein modeling and biophysical analysis indicated that Der p 13 adopts a β-barrel structure with a predominately apolar pocket representing a potential binding site for hydrophobic ligands. Fluorescent lipid-binding assays confirmed that the protein is highly selective for ligands and that it binds a fatty acid with a dissociation constant typical of lipid transporter proteins. The low IgE-binding frequency (7%, n = 224) in Thai HDM-allergic patients as well as the limited propensity to activate basophil degranulation classifies Der p 13 as a minor HDM allergen. Nevertheless, the protein with its presumptively associated lipid(s) triggered the production of IL-8 and GM-CSF in respiratory epithelial cells through a TLR2-, MyD88-, NF-kB-, and MAPK-dependent signaling pathway.
  
  
  
  Although a minor allergen, Der p 13 may, through its lipid-binding capacity, play a role in the initiation of the HDM-allergic response through TLR2 activation.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine; and Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Satitsuksanoa
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kennedy
authors.affiliation: BIO-Bioinfo Department, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Gilis
authors.affiliation: Stallergenes Greer, Antony, France.
authors.forename: M
authors.initials: M
authors.lastname: Le Mignon
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Suratannon
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine; and Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: W T
authors.initials: WT
authors.lastname: Soh
authors.affiliation: Center of Excellence in Immunology and Immune Mediated Diseases, Division of Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: J
authors.initials: J
authors.lastname: Wongpiyabovorn
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Chatchatee
authors.affiliation: Allergy, Immunology and Rheumatology Unit, Queen Sirikit National Institute of Child Health, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand.
authors.forename: M
authors.initials: M
authors.lastname: Vangveravong
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: T
authors.initials: T
authors.lastname: Rerkpattanapipat
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Sangasapaviliya
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Piboonpocanun
authors.affiliation: Stallergenes Greer, Antony, France.
authors.forename: E
authors.initials: E
authors.lastname: Nony
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine; and Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine; and Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. alain.j@chula.ac.th.
authors.forename: A
authors.initials: A
authors.lastname: Jacquet
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology; D050356:Lipid Metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D051195:Toll-Like Receptor 2; D007073:Immunoglobulin E
keywords: Der p 13; IgE reactivity; TLR2; allergen; house dust mite; innate immunity; lipid-binding protein