Unique and Cross-Reactive T Cell Epitope Peptides of the Major Bahia Grass Pollen Allergen, Pas n 1

Etto, Tamara Louise; Boer, Carmela Maria De; Prickett, Sara; Gardner, Leanne Margaret; Voskamp, Astrid; Davies, Janet M.; O’Hehir, Robyn E; Rolland, Jennifer M.

doi:10.1159/000338290

Cited by 25 publications

(17 citation statements)

References 66 publications

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“…1). Although dominant allergen epitopes are most simply defined as being those peptides/regions most frequently recognized within the respective allergen sequence 55–59, we considered a number of factors in addition to TCL responder frequencies to further refine our selection of epitopes for inclusion in a therapeutic. These included the magnitude of TCL response, number of specific TCL per subject, reproducibility of specific TCL response and ability to target specific T cells in PBMC.…”

Section: Resultsmentioning

confidence: 99%

Ara h 1 CD4+ T cell epitope‐based peptides: candidates for a peanut allergy therapeutic

Prickett

Voskamp

Phan

et al. 2013

Clin Experimental Allergy

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BackgroundPeanut allergy is a life-threatening condition; there is currently no cure. While whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions and even fatalities in peanut allergy.ObjectiveTo identify short, HLA-degenerate CD4+ T cell epitope-based peptides of the major peanut allergen Ara h 1 that target allergen-specific T cells without causing IgE-mediated inflammatory cell activation, as candidates for safe peanut-specific immunotherapy.MethodsAra h 1-specific CD4+ T cell lines (TCL) were generated from peripheral blood mononuclear cells (PBMC) of peanut-allergic subjects using CFSE-based methodology. T cell epitopes were identified using CFSE and thymidine-based proliferation assays. Epitope HLA-restriction was investigated using blocking antibodies, HLA-genotyping and epitope prediction algorithms. Functional peanut-specific IgE reactivity to peptides was assessed by basophil activation assay.ResultsA total of 145 Ara h 1-specific TCL were generated from 18 HLA-diverse peanut-allergic subjects. The TCL recognized 20-mer peptides throughout Ara h 1. Nine 20-mers containing the most frequently recognized epitopes were selected and their recognition confirmed in 18 additional peanut-allergic subjects. Ten core epitopes were mapped within these 20-mers. These were HLA-DQ and/or HLA–DR restricted, with each presented on at least two different HLA-molecules. Seven short (≤ 20 aa) non-basophil-reactive peptides encompassing all core epitopes were designed and validated in peanut-allergic donor PBMC T cell assays.Conclusions and Clinical RelevanceShort CD4+ T cell epitope-based Ara h 1 peptides were identified as novel candidates for a safe, T cell targeted peanut-specific immunotherapy for HLA-diverse populations.

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Section: Resultsmentioning

confidence: 99%

Ara h 1 CD4+ T cell epitope‐based peptides: candidates for a peanut allergy therapeutic

Prickett

Voskamp

Phan

et al. 2013

Clin Experimental Allergy

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“…Assessment of patients receiving temperate GP sublingual immunotherapy (SLIT) tablets showed lowered mean AR medication prescriptions and lower proportions of new onset of asthma than the non‐AIT‐treated groups . However, currently available AIT is not standardised for subtropical GP, which may be important for efficacious treatment of people who are primarily allergic to Panicoideae and/or Chloridoideae GP, given that only one of three T‐cell epitopes is shared between major allergens Pas n 1, Cyn d 1 and Lol p 1 . More specific assessment of GP sensitisation profiles, particularly in countries with multiple climatic zones, may serve to precisely identify the relevant GP to achieve the most efficacious treatment for an individual patient .…”

Section: Discussionmentioning

confidence: 99%

Biogeographical variation in specific IgE recognition of temperate and subtropical grass pollen allergens in allergic rhinitis patients

Kailaivasan

Timbrell

Solley³

et al. 2020

Clin & Trans Imm

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Objective Globally, grass pollens (GP) are major aeroallergen triggers of allergic rhinitis (AR) and asthma. However, patterns of allergic sensitisation to pollen of temperate (Pooideae: Lolium perenne) and subtropical (Chloridoideae: Cynodon dactylon and Panicoideae: Paspalum notatum) subfamilies in diverse climates remain unclear. This study aims to evaluate the level of allergic sensitisation and IgE specificity for major GP allergens representing the three subfamilies in biogeographically distinct regions. Methods Participants (GP‐allergic with AR, 330; non‐atopic, 29; other allergies, 54) were recruited in subtropical: Queensland, and temperate: New South Wales, Western and South Australia, regions. Clinical history, skin prick test (SPT), total and specific IgE to GP and purified allergens (ImmunoCAP) were evaluated. Cross‐inhibition of sIgE with Pas n 1, Cyn d 1 and Lol p 1 by GP extracts was investigated. Results Queensland participants showed higher sensitisation to P. notatum and C. dactylon than L. perenne GP. sIgE was higher to Pas n 1 and Cyn d 1, and sIgE to Pas n 1 and Cyn d 1 was inhibited more by Panicoideae and Chloridoideae, respectively, than Pooideae GP. Conversely, participants from temperate regions showed highest sensitisation levels to L. perenne GP and Lol p 1, and sIgE to Lol p 1 was inhibited more by Pooideae than other GP. Conclusion Levels and patterns of sensitisation to subtropical and temperate GP in AR patients depended on biogeography. Knowledge of the specificity of sensitisation to local allergens is important for optimal diagnosis and choice of allergen‐specific immunotherapy to maximise benefit.

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“…TCC from nonallergic individuals differed, however, from TCC of allergic individuals with respect to their low IL-4/IFN-γ ratio [91,92]. Nevertheless, the value of identifying major T cell epitopes, also from newly identified sources [93], should not be underestimated [94]. It provides a rational basis for the design of modern vaccines for specific immunotherapy which lack potential disease-aggravating, T cell-activating sequences.…”

Section: T Cell Model Systems For Allergy Researchmentioning

confidence: 99%

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Neunkirchner

Schmetterer

Pickl

2014

Int Arch Allergy Immunol

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During the last decades, a multitude of studies applying distinct in vitro and in vivo model systems have contributed greatly to our better understanding of the initiation and regulation of inflammatory processes leading to allergic diseases. Over the years, it has become evident that among lymphocytes, not only IgE-producing B cells and allergy-orchestrating CD4⁺ helper cells but also cytotoxic CD8⁺ T cells, γδ-T cells and innate lymphoid cells, as well as regulatory lymphocytes, might critically shape the immune response towards usually innocuous allergens. In this review, we provide a historic overview of pioneering work leading to the establishment of important lymphocyte-based model systems for allergy research. Moreover, we contrast the original findings with our currently more refined knowledge to appreciate the actual validity of the respective models and to reassess the conclusions obtained from them. Conflicting studies and interpretations are identified and discussed. The tables are intended to provide an easy overview of the field not only for scientists newly entering the field but also for the broader readership interested in updating their knowledge. Along those lines, herein we discuss in vitro and in vivo approaches to the investigation of lymphocyte effector cell activation, polarization and regulation, and describe depletion and adoptive transfer models along with gene knockout and transgenic (tg) methodologies. In addition, novel attempts to establish humanized T cell antigen receptor tg mouse models for allergy research are described and discussed.

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Unique and Cross-Reactive T Cell Epitope Peptides of the Major Bahia Grass Pollen Allergen, Pas n 1

Cited by 25 publications

References 66 publications

Ara h 1 CD4+ T cell epitope‐based peptides: candidates for a peanut allergy therapeutic

Ara h 1 CD4+ T cell epitope‐based peptides: candidates for a peanut allergy therapeutic

Biogeographical variation in specific IgE recognition of temperate and subtropical grass pollen allergens in allergic rhinitis patients

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

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