Type I allergy is an immunoglobulin E IgE -mediated chronic disease. As such, disease diagnosis and identification of targeted allergens are primarily based on specific IgE reactivity. Over the past decades, the contribution of T cells in allergy pathogenesis has been extensively studied. Cslls cells are not only significant for the onset and maintenance of allergic disease but likely also play a key role for the induction of tolerance by allergen-specific immunotherapy AIT. Due to the complexity of allergic T cell responses, epitopes have only been thoroughly mapped for the most dominant and prevalent allergens.
ASCL2 Achaete-scute homologue 2. BCL-6 B-cell lymphoma 6. CCR6 CC chemokine receptor type 6. CNS Conserved non-coding sequences. DAMP Damage-associated molecular pattern. T FH Follicular helper T. GC Germinal center. HDM House dust mite. IgE Immunoglobulin E. IRF4 Interferon regulatory factor 4.
This decrease in the concentration of the dye can be visualized by flow cytometry. Another approach is to stain stimulated cells with antibodies targeting markers associated with proliferation, such as Ki The measure of proliferation in response to antigen stimulation is straightforward and inexpensive.
The greatest caveat associated with using proliferation as a readout for antigen-specific reactivity is the relatively high rate of false positivity due to bystander activation. Al,ergy study designed to directly compare the use of tetramer staining reagents versus allergen-induced proliferation for the detection of allergen-specific T cells found that while tetramers had a relatively low rate of sensitivity, cells allergy based on proliferation contained extremely high fractions of bystander cells [ 34 ], making this approach cells suitable if an enriched population is sufficient for the study rather than a desire for a pure antigen-specific population.
Allergy and asthma are debilitating diseases that are most commonly treated using pharmacotherapy which are designed to improve the symptoms but not the cause of disease.
To date, the only disease-modifying therapy available is allergen-specific immunotherapy Cells. First administered over a century ago [ 47 eclls, AIT has been widely demonstrated to be a clinically effective treatment, inducing immunological tolerance and improvement of clinical symptoms beyond the time of treatment [ 48 ].
Despite its favorable duration of efficacy, a considerable effort is invested to improve current AIT protocols. The occurrence of such adverse events and the need for extended treatment periods that last several years can have a negative impact on treatment compliance. For this reason, researchers have strived to find a treatment that targets G cells and circumvents potential IgE reactivity. Removal ce,ls IgE epitopes, thereby eliminating the risk of IgE cross-linking, is one obvious approach.
Aloergy are a variety of methods to achieve this goal, some of which have been evaluated cells clinical alletgy. One allergy pursued approach for AIT focused on T cells while omitting IgE epitopes is called peptide immunotherapy, where instead of using whole allergen extract, allergic patients are treated with a mixture of short, synthetic peptides that constitute the major T cell epitopes of the allergen the patient is allergic to. The clinical efficacy of peptide immunotherapy crlls been demonstrated in several Phase IIb double-blind, placebo-controlled trials [ 4950 ].
A significant reduction in symptoms, measured as the total rhinoconjunctivitis symptom score TRSSwas observed following the administration of allergy eight intradermal injections of the peptide formulation. In this study, TRSS levels remained suppressed both at the 1- and 2-year follow-up time point [ 51 ].
The immunological cells by which peptide immunotherapy induces tolerance are not yet fully understood. However, studies have reported a downregulation of pathological type 2 cell responses and a concomitant increase in regulatory signals, such as the production of IL in the periphery.
The induction of Allergy antibodies, which are believed to contribute to clinical efficacy by occupying the allergen-binding sites, thereby preventing IgE-allergen binding, is a hallmark event during conventional AIT with allergen extract.
Interestingly, increased levels of IgG4 are rarely observed, probably due cels the lack of conformational B cell epitopes decreasing the likelihood of B cell stimulation and resulting IgG production.
Therefore, though modulatory events on the cellular level appear to be broadly similar to those believed to occur during extract-based AIT, humoral responses may be more distinct. Although peptide immunotherapy has been shown to be clinically effective, it is also associated with challenges that need to be addressed. The route of administration has been debated, and the clinical effects seem to be very sensitive to dosing.
Lower doses may not induce tolerance due to lack of potency for induction of regulatory T cells, while too allergy dose may stimulate and expand pathogenic Th2 cells. The selection of peptides is also a factor of consideration.
Typically, mixtures used for peptide immunotherapy include between 5 and 10 peptides. However, epitope specificities can be very heterologous in a given population, and therefore the selection may not be straightforward.
The consideration of these factors and others make the development of peptide immunotherapy challenging at times. Another approach of AIT that was designed to target T cells while bypassing IgE binding to avoid IgE-mediated side effects is the generation of fragmented allergens. This approach was tested using the major birch pollen allergen, Bet v 1, as a model.
The fragmentation of the allergen involved its division into non-IgE-binding fragments, which retain their T cell reactivity. Birch pollen allergic patients were then vaccinated with these hypoallergenic derivatives in cells double-blind, placebo-controlled allegry.
This vaccination was found to reduce cutaneous sensitivity, improve symptoms, and significantly reduce rises in birch-specific IgE levels during season in the active group compared to placebo [ 52 ]. However, immunological mechanisms and long-term efficacy were not evaluated.
Allergic disease severity is very poorly understood. The degree of symptom manifestation, such as asthma versus rhinitis can often not be explained by allergen-specific IgE titers. There is a dire need for better diagnostics and biomarkers that will help us evaluate treatment options and disease prognosis. Gaining a better understanding allrgy the immunological events on a cellular level may have a tremendous impact on how we treat patients in the clinic.
However, performing such experiments in the clinic allergy not feasible. Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Edited by Seyyed Shamsadin Athari.
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Downloaded: Keywords allergy T cells Th2 IgE epitope. Challenges of T cell epitope mapping The identification of T cell epitopes from major allergens is an important goal allergy allergy research. Overlapping versus predicted peptide To identify T cell epitopes in allergy, the most diligent approach involves testing overlapping peptides that span the entire sequence of the allergen of interest.
Allergen-specific T cell frequencies Another challenging aspect of T cell epitope identification in allergy is the low frequency of allergen-specific T cells.
T follicular helper and TH2 cells in allergic responses - ScienceDirect
Immunological characterization of allergen-specific T cells There are several approaches to isolate allergen-specific cells ex vivo for subsequent downstream immunological profiling using technologies, such as RNA or TCR sequencing. MHC tetramer assay The use of MHC tetramer reagents to detect antigen-specific T 22 is a well-established technique that allows detection and further downstream analysis of allergen-specific cells on a single cell level.
Cytokine capture assay The isolation of allergy cells based on cytokine production used to be complicated by the fact that T cells positive for cytokine production were detected by intracellular cytokine staining, which involved cells and permeabilization of the cell.
Cell cekls assays Another hallmark of antigen-specific T cells is the upregulation of activation markers in response to antigen stimulation.
Proliferation assays The identification of antigen-specific cells based on the proliferative response to antigenic stimulation is perhaps the most allerggy approach and has been widely used for several applications including T cell epitope mapping, phenotypic characterization, T cell response kinetics, and others.
Targeting T cells in allergen-specific immunotherapy Allergy and asthma are debilitating diseases that are most commonly treated using pharmacotherapy which are designed to improve the symptoms but not the cause of disease.
Peptide immunotherapy One extensively pursued approach for AIT focused on T cells while omitting IgE epitopes is called peptide immunotherapy, where instead of using whole allergen extract, allergic patients are treated with a mixture of short, synthetic peptides that constitute the major T cell epitopes of the allergen the patient is allergic to.
Fragmented allergens Another approach of AIT that was designed to target T cells while bypassing IgE cells to avoid IgE-mediated side effects is the generation of fragmented allergens. Concluding remarks Allergic disease severity is very poorly understood. How to cite and reference Link to this chapter Copy to clipboard. Global Initiative for Asthma. Archived from the original PDF on 17 October Archived from the original PDF on July Grammer Patterson's Allergic Diseases 7 ed.
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Angioedema Urticaria Atopic dermatitis Allergic contact dermatitis Hypersensitivity vasculitis.
Serum sickness. Coeliac disease Eosinophilic gastroenteritis Eosinophilic esophagitis Food allergy Egg allergy Milk intolerance. Eosinophilic meningitis.