Peanut-specific T cell responses in patients with different clinical reactivity

PLoS One. 2018 Oct 10;13(10):e0204620. doi: 10.1371/journal.pone.0204620. eCollection 2018.

Abstract

Whole extract or allergen-specific IgE testing has become increasingly popular in the diagnosis of peanut allergy. However, much less is known about T cell responses in peanut allergy and how it relates to different clinical phenotypes. CD4+ T cells play a major role in the pathophysiology of peanut allergy as well as tolerance induction during oral desensitization regimens. We set out to characterize and phenotype the T cell responses and their targets in peanut sensitized patients. Using PBMC from peanut-allergic and non-allergic patients, we mapped T cell epitopes for three major peanut allergens, Ara h 1, 2 and 3 (27 from Ara h 1, 4 from Ara h 2 and 43 from Ara h 3) associated with release of IFNγ (representative Th1 cytokine) and IL5 (representative Th2 cytokine). A pool containing 19 immunodominant peptides, selected to account for 60% of the total Ara h 1-3-specific T cell response in allergics, but only 20% in non-allergics, was shown to discriminate T cell responses in peanut-sensitized, symptomatic vs non-symptomatic individuals more effectively than peanut extract. This pool elicited positive T cell responses above a defined threshold in 12/15 sensitized, symptomatic patients, whereas in the sensitized but non-symptomatic cohort only, 4/14 reacted. The reactivity against this peptide pool in symptomatic patients was dominated by IL-10, IL-17 and to a lesser extend IL-5. For four distinct epitopes, HLA class II restrictions were determined, enabling production of tetrameric reagents. Tetramer staining in four donors (2 symptomatic, 2 non-symptomatic) revealed a trend for increased numbers of peanut epitope-specific T cells in symptomatic patients compared to non-symptomatic patients, which was associated with elevated CRTh2 expression whereas cells from non-symptomatic patients exhibited higher levels of Integrin β7 expression. Our results demonstrate differences in T cell response magnitude, epitope specificity and phenotype between symptomatic and non-symptomatic peanut-sensitized patients. In addition to IgE reactivity, analysis of peanut-specific T cells may be useful to improve our understanding of different clinical manifestations in peanut allergy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, Plant / immunology*
  • Arachis / immunology*
  • Cells, Cultured
  • Cohort Studies
  • Epitope Mapping
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Interferon-gamma / blood
  • Interleukin-5 / blood
  • Male
  • Peanut Hypersensitivity / blood
  • Peanut Hypersensitivity / immunology*
  • Receptors, Immunologic / blood
  • Receptors, Prostaglandin / blood
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Plant
  • IFNG protein, human
  • IL5 protein, human
  • Interleukin-5
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Immunoglobulin E
  • Interferon-gamma
  • prostaglandin D2 receptor