| Affiliations | Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom; Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom; Department of Allergy and Immunology, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom. | |
| Abstract | BACKGROUND: Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic mice. METHODS: Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic mice.Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis/asthma, n=25), non-HDM sensitised (atopic controls sensitised to ≥1 other aero-allergens, n=10) and non-atopic healthy controls, n=10). Peripheral blood mononuclear cells (PBMC) were collected and screened for immune responses to Der p 1 or test peptides A-E. Mapping of minimal T-cell epitopes, apitope (antigen-processing independent epitope) validation and tolerance induction were tested in HLA-DR transgenic mice. RESULTS: Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic mice.Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis/asthma, n=25), non-HDM sensitised (atopic controls sensitised to ≥1 other aero-allergens, n=10) and non-atopic healthy controls, n=10). Peripheral blood mononuclear cells (PBMC) were collected and screened for immune responses to Der p 1 or test peptides A-E. Mapping of minimal T-cell epitopes, apitope (antigen-processing independent epitope) validation and tolerance induction were tested in HLA-DR transgenic mice.HDM-sensitised subjects have an elevated response to pan-DR binding peptide D 30mer. Peptide analogue D121B, containing the minimal epitope and optimised for solubility, was verified as a tolerogenic apitope and induced tolerance against Der p 1 antigens in HLA-DR4 transgenic mice . CONCLUSION: Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic mice.Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis/asthma, n=25), non-HDM se... | |