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J Allergy Clin Immunol. 2016 Aug;138(2):571-578.e7. doi: 10.1016/j.jaci.2015.11.034. Epub 2016 Feb 13.

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

Author information

  • 1La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
  • 2Laboratory of Cellular Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland.
  • 3Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
  • 4Laboratory 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.
  • 5La Jolla Institute for Allergy and Immunology, La Jolla, Calif. Electronic address: bpeters@liai.org.

Abstract

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.

KEYWORDS:

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

PMID:
26883464
PMCID:
PMC4975972
[Available on 2017-08-01]
DOI:
10.1016/j.jaci.2015.11.034
[PubMed - in process]
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