title: Oral treatment with β-lactoglobulin peptides prevents clinical symptoms in a mouse model for cow's milk allergy.
abstract: BACKGROUND
  Prior exposure to partial whey hydrolysates has been shown to reduce the allergic response to whey in mice. This effect was more pronounced in combination with a diet containing non-digestible oligosaccharides (scGOS/lcFOS/pAOS). It is unknown which fractions/epitopes are responsible for this effect. Therefore, the prophylactic ability of synthetic peptides of β-lactoglobulin with/without a scGOS/lcFOS/pAOS-containing diet to reduce the allergic response in a mouse model for cow's milk allergy was investigated.
  
  
  METHODS
  Of 31 peptides, nine peptides were selected based on human T cell data. Mice were pre-treated orally with three peptide mixtures or single peptides for six consecutive days. During this period, they received a control or scGOS/lcFOS/pAOS-containing diet. Subsequently, mice were orally sensitized to whey and received an intradermal and oral challenge. After sacrifice, serum and mesenteric lymph nodes (MLN) were collected for further analysis.
  
  
  RESULTS
  Prior exposure to peptide mixtures 1 and 3 significantly reduced the acute allergic skin response to whey. Mixture 2 showed no effect. An additive effect of the scGOS/lcFOS/pAOS-containing diet was only observed for mixture 1. Of the peptides in mixture 1, one peptide (LLDAQSAPLRVYVEELKP) showed the strongest effect on the acute allergic skin response. This peptide also tended to decrease whey-specific antibody levels and to increase the percentages of CD11b+CD103+ dendritic cells and CD25+Foxp3+ T cells in the MLN.
  
  
  CONCLUSIONS
  Prior exposure to specific peptides of β-lactoglobulin reduces the allergic response to whey, which may involve regulatory dendritic and T cells. Combining peptides with a sGOS/lcFOS/pAOS-containing diet enhances this effect.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Laura A P M
authors.initials: LA
authors.lastname: Meulenbroek
authors.forename: Betty C A M
authors.initials: BC
authors.lastname: van Esch
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Hofman
authors.forename: Constance F
authors.initials: CF
authors.lastname: den Hartog Jager
authors.forename: Alma J
authors.initials: AJ
authors.lastname: Nauta
authors.forename: Linette E M
authors.initials: LE
authors.lastname: Willemsen
authors.forename: Carla A F M
authors.initials: CA
authors.lastname: Bruijnzeel-Koomen
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Els
authors.initials: E
authors.lastname: van Hoffen
authors.forename: Léon M J
authors.initials: LM
authors.lastname: Knippels
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007782:Lactoglobulins / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D016269:Milk Hypersensitivity / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D007782:Lactoglobulins; D009844:Oligosaccharides; D010446:Peptide Fragments
keywords: CD103+ dendritic cells; T cell epitopes; animal model; cow's milk allergy; non-digestible oligosaccharides; oral tolerance; peptides; prophylaxis; regulatory T cells; β-lactoglobulin