title: Sequence conservation predicts T cell reactivity against ragweed allergens.
abstract: Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied.
  
  
  
  We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens.
  
  
  
  Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-γ (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed.
  
  
  
  Three previously identified dominant T cell epitopes (Amb a 1 176-191, 200-215, and 344-359) were confirmed, and three novel dominant epitopes (Amb a 1 280-295, 304-319, and 320-335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens.
  
  
  
  These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pham
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Oseroff
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hinz
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Paul
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Greenbaum
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vita
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Phillips
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mallal
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Peters
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D031164:Ambrosia / Q000009:adverse effects* / Q000235:genetics*; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006650:Histocompatibility Testing; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010455:Peptides; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: T cell epitopes; allergens; ragweed