The identification of potentially pathogenic and therapeutic epitopes from common human allergens

Schulten, Véronique; Oseroff, Carla; Alam, Rafeul; Broide, David H.; Vijayanand, Pandurangan; Peters, Bjoern; Sette, Alessandro

doi:10.1016/j.anai.2012.10.015

Cited by 9 publications

(16 citation statements)

References 46 publications

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“…Unlike some autoimmune conditions, allergic diseases generally are not closely linked with particular HLA types . Reflecting this fact, allergen T cell epitopes often demonstrate extensive HLA‐binding degeneracy and, in turn, allergen‐specific CD4 + T cells may recognize a particular epitope complexed with several different HLA class II molecules . Importantly, whilst nominal antigens are most commonly presented on HLA‐DR molecules, many allergen T cell epitopes have been shown to also be presented on HLA‐DQ and HLA‐DP molecules .…”

Section: Hla Class II Restriction Of T Cell Recognition Of Allergen Pmentioning

confidence: 99%

Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy

Prickett

Rolland

O’Hehir

2015

Clin Experimental Allergy

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Allergen immunotherapy (AIT) has been practised since 1911 and remains the only therapy proven to modify the natural history of allergic diseases. Although efficacious in carefully selected individuals, the currently licensed whole allergen extracts retain the risk of IgE-mediated adverse events, including anaphylaxis and occasionally death. This together with the need for prolonged treatment regimens results in poor patient adherence. The central role of the T cell in orchestrating the immune response to allergen informs the choice of T cell targeted therapies for down-regulation of aberrant allergic responses. Carefully mapped short synthetic peptides that contain the dominant T cell epitopes of major allergens and bind to a diverse array of HLA class II alleles, can be delivered intradermally into non-inflamed skin to induce sustained clinical and immunological tolerance. The short peptides from allergenic proteins are unable to cross-link IgE and possess minimal inflammatory potential. Systematic progress has been made from in vitro human models of allergen T cell epitope-based peptide anergy in the early 1990s, through proof-of-concept murine allergy models and early human trials with longer peptides, to the current randomized, double-blind, placebo-controlled clinical trials with the potential new class of synthetic short immune-regulatory T cell epitope peptide therapies. Sustained efficacy with few adverse events is being reported for cat, house dust mite and grass pollen allergy after only a short course of treatment. Underlying immunological mechanisms remain to be fully delineated but anergy, deletion, immune deviation and Treg induction all seem contributory to successful outcomes, with changes in IgG4 apparently less important compared to conventional AIT. T cell epitope peptide therapy is promising a safe and effective new class of specific treatment for allergy, enabling wider application even for more severe allergic diseases.

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Section: Hla Class II Restriction Of T Cell Recognition Of Allergen Pmentioning

confidence: 99%

Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy

Prickett

Rolland

O’Hehir

2015

Clin Experimental Allergy

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“…T R 1 cells secreting IL-10 have been implicated in negative regulation of T cell allergic responses (27). The balance between T H 2 cells and IFNγ-producing T H 1 cells (T H 1/T H 2 polarization) is considered a potential key determinant in regulating allergic disease (1,28). Finally, recent studies have described T FH cells, associated with production of IL-21, as key regulators of isotype switch (including IgE) (29).…”

Section: Introductionmentioning

confidence: 99%

Different Bla‐g T cell antigens dominate responses in asthma versus rhinitis subjects

Dillon

Schulten

Oseroff

et al. 2015

Clin Experimental Allergy

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Background and Objective The allergenicity of several German cockroach (Bla-g) antigens at the level of IgE responses is well established. However less is known about the specificity of CD4+ TH responses, and whether differences exist in associated magnitude or cytokine profiles as a function of disease severity. Methods Proteomic and transcriptomic techniques have been employed to identify novel antigens recognized by allergen-specific T cells. To characterize different TH functionalities of allergen-specific T cells, ELISPOT assays with sets of overlapping peptides covering the sequences of known allergens and novel antigens were employed to measure release of IL-5, IFNγ, IL-10, IL-17, and IL-21. Results Using these techniques, we characterized TH responses in a cohort of adult Bla-g sensitized subjects, either with (n=55) or without (n=17) asthma, and non-sensitized controls (n=20). T cell responses were detected for ten known Bla-g allergens and an additional ten novel Bla-g antigens; representing in total a 5-fold increase in the number of antigens demonstrated to be targeted by allergen-specific T cells. Responses of sensitized individuals regardless of asthma status were predominantly TH2, but higher in patients with diagnosed asthma. In asthmatic subjects Bla-g 5, 9 and 11 were immunodominant while, in contrast, non-asthmatic sensitized subjects responded mostly to Bla-g 5, 4, and the novel antigen NBGA5. Conclusions Asthmatic and non-asthmatic cockroach sensitized individuals exhibit similar TH2 polarized responses. Compared to non-asthmatics, however, asthmatic individuals have responses of higher magnitude and different allergen specificity.

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“…However, other peptides may induce opposing or dampened Th2 responses by stimulating Th1 or regulatory cytokine responses, respectively. 27 Oseroff et al characterized T cell responses to epitopes derived from several Bla g allergens among 34 adults with allergic rhinitis or asthma who were also cockroach sensitive. 28 Responses to 25 distinct antigenic peptide epitopes were identified.…”

Section: Recombinant Techniques May Improve the Efficacy Of Cockroachmentioning

confidence: 99%

Cockroach allergy and allergen-specific immunotherapy in asthma

Bassirpour

Zoratti

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review To provide a summary and discussion of cockroach allergy and clinical trials of cockroach allergen immunotherapy. Recent findings Cockroach allergen exposure among sensitized children is increasingly recognized as a key factor contributing to asthma morbidity. Recent trials suggest that cockroach immunotherapy has promise as a treatment strategy with studies demonstrating immunomodulatory and clinical effects. However, a few obstacles need to be overcome to realize the full potential of this treatment modality as cockroach allergic patients often exhibit complex sensitization patterns to multiple cockroach-associated proteins and an immunodominant allergen has not been identified. These factors have made it difficult to produce standardized cockroach allergen extracts that are potent and provide the broad allergen profiles needed for optimal treatment. There have been important advances in the identification and cloning of cockroach allergens and several strategies are being developed to provide therapeutic cockroach allergen products with enhanced clinical efficacy. Summary Allergen immunotherapy has the capability of modulating the immune response to cockroach allergen and has potential as a valuable treatment modality. Further studies of the clinical efficacy along with the development of improved therapeutic products are needed to advance our knowledge and realize the full potential of this promising therapy.

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The identification of potentially pathogenic and therapeutic epitopes from common human allergens

Cited by 9 publications

References 46 publications

Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy

Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy

Different Bla‐g T cell antigens dominate responses in asthma versus rhinitis subjects

Cockroach allergy and allergen-specific immunotherapy in asthma

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