title: T-cell epitope conservation across allergen species is a major determinant of immunogenicity.
abstract: Patients with pollen allergies are frequently polysensitized. Pollens contain epitopes that are conserved across multiple species.
  
  
  
  We sought to demonstrate that cross-reactive T cells that recognize conserved epitopes show higher levels of expansion than T cells recognizing monospecific epitopes because of more frequent stimulation.
  
  
  
  RNA was sequenced from 9 pollens, and the reads were assembled de novo into more than 50,000 transcripts. T-cell epitopes from timothy grass (Phleum pratense) were examined for conservation in these transcripts, and this was correlated to their ability to induce T-cell responses. T cells were expanded in vitro with P pratense-derived peptides and tested for cross-reactivity to pollen extracts in ELISpot assays.
  
  
  
  We found that antigenic proteins are more conserved than nonimmunogenic proteins in P pratense pollen. Additionally, P pratense epitopes that were highly conserved across pollens elicited more T-cell responses in donors with grass allergy than less conserved epitopes. Moreover, conservation of a P pratense peptide at the transcriptomic level correlated with the ability of that peptide to trigger T cells that were cross-reactive with other non-P pratense pollen extracts.
  
  
  
  We found a correlation between conservation of peptides in plant pollens and their T-cell immunogenicity within P pratense, as well as their ability to induce cross-reactive T-cell responses. T cells recognizing conserved epitopes might be more prominent because they can be stimulated by a broader range of pollens and thereby drive polysensitization in allergic donors. We propose that conserved peptides could potentially be used in diagnostic or immunomodulatory approaches that address the issue of polysensitization and target multiple pollen allergies.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Luise
authors.initials: L
authors.lastname: Westernberg
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Véronique
authors.initials: V
authors.lastname: Schulten
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Greenbaum
authors.affiliation: Laboratory of Cellular Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Natali
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Victoria
authors.initials: V
authors.lastname: Tripple
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Denise M
authors.initials: DM
authors.lastname: McKinney
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: April
authors.initials: A
authors.lastname: Frazier
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hofer
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Wallner
authors.affiliation: Laboratory of Cellular Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland; Center of Medical Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, Calif. Electronic address: bpeters@liai.org.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
mesh_terms: D000328:Adult; D000485:Allergens / Q000235:genetics / Q000276:immunology*; D052179:Antigens, Plant / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D003429:Cross Reactions / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000235:genetics / Q000276:immunology; D011058:Pollen / Q000235:genetics / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D007073:Immunoglobulin E
keywords: RNA sequencing; T cell; cross-reactivity; epitope; pollen allergy; sequence conservation; timothy grass allergy; transcriptome