title: Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4(+) T cell epitopes with other tree nuts.
abstract: Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T cell epitopes and T cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized.
  
  
  
  In this study, we characterized cashew-specific T cell responses in cashew-allergic subjects and examined cross-reactivity of these cashew-specific cells towards other tree nut allergens.
  
  
  
  CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T cells were determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts.
  
  
  
  CD4(+) T cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T cell epitopes were then identified. These epitopes elicited either TH 2 or TH 2/TH 17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut.
  
  
  
  Phylogenetically diverse tree nut allergens can activate cashew-reactive T cells and elicit a TH 2-type response at an epitope-specific level.
  
  
  
  Lack of cross-reactivity between walnut and cashew suggests that cashew peptide immunotherapy approach may not be most effective for walnut.
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Archila
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: I-T
authors.initials: IT
authors.lastname: Chow
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: McGinty
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Renand
authors.affiliation: Virginia Mason Medical center, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Virginia Mason Medical center, Seattle, WA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Virginia Mason Medical center, Seattle, WA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Farrington
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000276:immunology*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D003429:Cross Reactions / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D021184:Nut Hypersensitivity / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009754:Nuts / Q000009:adverse effects*; D010940:Plant Proteins / Q000276:immunology*; D012882:Skin Tests; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000485:Allergens; C464614:Ana o 1 protein, Anacardium occidental; C478880:Ana o 2 allergen, cashew; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: Ana o 1; Ana o 2; MHC class II tetramers; T cells; cashew; cross-reactivity; epitopes; food allergy; tree nuts