T-cell epitope conservation across allergen species is a major determinant of immunogenicity

Autor: Denise M. McKinney, Michael Wallner, April Frazier, Sara Natali, Victoria Tripple, Heidi Hofer, Jason A. Greenbaum, Alessandro Sette, Luise Westernberg, Bjoern Peters, Federica Sallusto, Veronique Schulten
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
cross-reactivity
T-Lymphocytes
Epitopes
T-Lymphocyte
medicine.disease_cause
Cross-reactivity
Epitope
Conserved sequence
0302 clinical medicine
Immunology and Allergy
Conserved Sequence
epitope
Timothy-grass
biology
Immunogenicity
food and beverages
RNA sequencing
Middle Aged
medicine.anatomical_structure
Pollen
Female
sequence conservation
Adult
T cell
Immunology
timothy grass allergy
Cross Reactions
Poaceae
Article
Microbiology
Evolution
Molecular
Phleum
Young Adult
03 medical and health sciences
Antigen
pollen allergy
otorhinolaryngologic diseases
medicine
Humans
Gene Expression Profiling
Rhinitis
Allergic
Seasonal
Sequence Analysis
DNA
Allergens
Antigens
Plant
Immunoglobulin E
biology.organism_classification
030104 developmental biology
Transcriptome
030215 immunology
Zdroj: Journal of Allergy and Clinical Immunology. 138:571-578.e7
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2015.11.034
Popis: Background Patients with pollen allergies are frequently polysensitized. Pollens contain epitopes that are conserved across multiple species. Objective 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. Method 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. Results 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. Conclusion 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.
Databáze: OpenAIRE
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