{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:36:18Z","timestamp":1781804178747,"version":"3.54.5"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted <jats:italic>in silico<\/jats:italic> and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis\/asthma, n=25), non-HDM sensitised (atopic controls sensitised to \u22651 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A tolerogenic peptide, apitope D121B, reduces T-cell immune responses to Der p 1 and is a promising candidate for further development as an immunotherapy for HDM-associated allergic rhinitis and asthma.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1569283","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:13:33Z","timestamp":1744348413000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A dominant, pan-DR binding epitope of Der p 1 in house dust mite allergy induces tolerance in HLA-DR4 transgenic mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Heather B.","family":"Streeter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora G.","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamidipudi T.","family":"Krishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Wraith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaci.2014.10.012","article-title":"Respiratory allergy caused by house dust mites: What do we really know","volume":"136","author":"Calderon","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12130","article-title":"Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution","volume":"12","author":"Savoure","year":"2022","journal-title":"Clin Transl Allergy"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01293.x","article-title":"Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I","volume":"62","author":"Bousquet","year":"2007","journal-title":"Allergy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18094945","article-title":"Exposures in the indoor environment and prevalence of allergic conditions in the United States of America","volume":"18","author":"Gasana","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.jaci.2009.12.018","article-title":"Toward improved prediction of risk for atopy and asthma among preschoolers: a prospective cohort study","volume":"125","author":"Holt","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.jaci.2011.06.038","article-title":"House dust mite sensitization in toddlers predicts current wheeze at age 12 years","volume":"128","author":"Lodge","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)78276-6","article-title":"Prophylactic innoculation against hay fever","author":"Noon","year":"1911","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jaci.2009.10.035","article-title":"Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet","volume":"125","author":"Durham","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2001.01161.x","article-title":"Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. 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