title: Identification of Maillard reaction products on peanut allergens that influence binding to the receptor for advanced glycation end products.
abstract: BACKGROUND
  Recent immunological data demonstrated that dendritic cells preferentially recognize advanced glycation end product (AGE)-modified proteins, upregulate expression of the receptor for AGE (RAGE), and consequently bias the immune response toward allergy.
  
  
  METHODS
  Peanut extract was characterized by mass spectrometry (MS) to elucidate the specific residues and specific AGE modifications found in raw and roasted peanuts and on rAra h 1 that was artificially glycated by incubation with glucose or xylose. The binding of the RAGE-V1C1 domain to peanut allergens was assessed by PAGE and Western analysis with anti-Ara h 1, 2, and 3 antibodies. IgE binding to rAra h 1 was also assessed using the same methods.
  
  
  RESULTS
  AGE modifications were found on Ara h 1 and Ara h 3 in both raw and roasted peanut extract. No AGE modifications were found on Ara h 2. Mass spectrometry and Western blot analysis demonstrated that RAGE binds selectively to Ara h 1 and Ara h 3 derived from peanut extract, whereas the analysis failed to demonstrate Ara h 2 binding to RAGE. rAra h 1 with no AGE modifications did not bind RAGE; however, after AGE modification with xylose, rAra h 1 bound to RAGE.
  
  
  CONCLUSIONS
  AGE modifications to Ara h 1 and Ara h 3 can be found in both raw and roasted peanuts. Receptor for AGE was demonstrated to selectively interact with AGE-modified rAra h 1. If sensitization to peanut allergens occurs in dendritic cells via RAGE interactions, these cells are likely interacting with modified Ara h 1 and Ara h 3, but not Ara h 2.
authors.affiliation: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Mueller
authors.forename: S J
authors.initials: SJ
authors.lastname: Maleki
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: B K
authors.initials: BK
authors.lastname: Hurlburt
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: S
authors.initials: S
authors.lastname: Ruan
authors.forename: J B
authors.initials: JB
authors.lastname: Nesbit
authors.forename: A
authors.initials: A
authors.lastname: Pomés
authors.forename: L L
authors.initials: LL
authors.lastname: Edwards
authors.forename: A
authors.initials: A
authors.lastname: Schorzman
authors.forename: L J
authors.initials: LJ
authors.lastname: Deterding
authors.forename: H
authors.initials: H
authors.lastname: Park
authors.forename: K B
authors.initials: KB
authors.lastname: Tomer
authors.forename: R E
authors.initials: RE
authors.lastname: London
authors.forename: J G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000276:immunology; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010367:Arachis / Q000737:chemistry* / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D015416:Maillard Reaction; D008565:Membrane Proteins; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D053719:Tandem Mass Spectrometry
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D008565:Membrane Proteins; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: advanced glycation end product; allergens; epitopes; peanuts; receptor for AGE