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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Westernberg, Luise¹  Schulten, Veronique¹  Greenbaum, Jason A.¹  Natali, Sara³  Tripple, Victoria¹  McKinney, Denise M.¹  Frazier, April¹  Hofer, Heidi²  Wallner, Michael²  Sallusto, Federica^3,4  Sette, Alessandro¹  Peters, Bjoern¹ 

[1] La Jolla Inst Allergy & Immunol, La Jolla, CA USA

[2] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria

[3] Univ Italian Switzerland, Cellular Immunol Lab, Inst Res Biomed, Bellinzona, Switzerland

[4] Univ Italian Switzerland, Ctr Med Immunol, Inst Res Biomed, Bellinzona, Switzerland

关键词: T cell;    epitope;    timothy grass allergy;    pollen allergy;    cross-reactivity;    RNA sequencing;    sequence conservation;    transcriptome;   

DOI  :  10.1016/j.jaci.2015.11.034

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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