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Deep TCR repertoire sequencing reveals relative change in peanut specific clonotype in subjects undergoing rush oral immunotherapy
Allergy, Asthma & Clinical Immunology volume 10, Article number: A53 (2014)
Oral immunotherapy is an emerging therapy currently under investigation for the treatment of food allergy . Underlying mechanisms are thought to involve a switch in the food specific T cell response from Th2 to either Th1, Tr1 and/or Treg. It is unknown whether this change in response results from re-education of existing pathological food-specific T cells or from their replacement by new healthy T cells (change of guard hypothesis).
The objective was to evaluate the clonal distribution of peanut specific T cell in subjects with peanut allergy and follow changes in clonotype with treatment using a high-throughput T cell receptor (TCR) sequencing platform. Peripheral blood mononuclear cells (PBMCs) from three subjects undergoing rush oral immunotherapy in a previous trial  and three control subjects on avoidance diet were cultured with peanut extract at baseline and at 9 and 18 months. Carboxyfluorescein succinimidyl ester (CFSE)-low peanut proliferating T cells were then isolated by fluorescence-activated cell sorting (FACS) and TCR analysis was performed.
The CFSE-low proliferating fraction was found to be comprised of between 2000 and 12,000 different T cell clones. However, only between 15 and 25% of proliferating T cells (from 100-400 different clones) were consistently found at all three time points and probably represented true peanut-specific T cells. While the relative frequency of these peanut-specific clones was stable over time in subjects on avoidance diet (R=0.633 to 0.760), it was found to change in subjects undergoing oral immunotherapy (R= 0.123 to 0.350), following two characteristic patterns.
Using a deep TCR sequencing platform, we found that only a fraction of CFSE-low peanut proliferating T cells were consistent in time and likely to represent true peanut specific T cells. Oral immunotherapy was associated with changes in relative frequency of clones within this fraction, which would support the change of guard hypothesis.
Bégin P, Chinthrajah RS, Nadeau KC: Oral immunotherapy for the treatment of food allergy. Hum Vaccin Immunother. 2014, 10: 8-
Bégin P, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, Trela A, Tavassoli M, Hoyte E, O’Riordan G, Blakemore A, Seki S, Hamilton RG, Nadeau KC: Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab. Allergy, Asthma & Clinical Immunology. 2014, 10: 7-10.1186/1710-1492-10-S1-A7.
P. Bégin was supported by AllerGen NCE Inc. (the Allergy, Gene and Environment Network), a member of the Networks of Centre of Excellence Canada program.
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Bégin, P., Nadeau, K.C. Deep TCR repertoire sequencing reveals relative change in peanut specific clonotype in subjects undergoing rush oral immunotherapy. All Asth Clin Immun 10, A53 (2014). https://doi.org/10.1186/1710-1492-10-S2-A53
- Peripheral Blood Mononuclear Cell
- Relative Frequency
- Food Allergy
- Sequencing Platform
- Response Result