{"doi":"10.1002/pro.70269","title":"Human <scp>IgE</scp> monoclonal antibodies define two unusual epitopes trapping dog allergen Can f 1 in different conformations","abstract":"Molecular analysis of interactions between IgE antibody and allergen allows the structural basis of IgE recognition to be defined. Human IgE (hIgE) epitopes of respiratory lipocalin allergens, including Can f 1, remain elusive due to a lack of IgE-allergen complexes. This study aims to map the structure of allergenic epitopes on Can f 1. The fragment antigen-binding (Fab) regions of Can f 1 specific human IgE monoclonal antibodies (hIgE mAb) were used to determine the structures of IgE epitopes. Epitope mutants were designed to target Can f 1 epitopes. Immunoassays and a human FcεRIα transgenic mouse model of passive anaphylaxis in vivo were used to assess the functional activity of epitope mutants. Crystal structures of natural or recombinant Can f 1 complexed with two hIgE mAb 1J11 and 12F3 Fabs, respectively, were determined. The hIgE mAb bound to two partially overlapping epitopes and recognized two different Can f 1 conformations. The hIgE mAb 12F3 showed an unusual mode of binding by protruding its heavy chain CDR3 inside the Can f 1 calyx. Epitope mutants generated based on the structural analyses displayed a 64%-89% reduction in IgE antibody binding and failed to induce passive anaphylaxis in a human FcεRIα transgenic mouse model. In summary, the structures of Can f 1-hIgE Fab complexes revealed two unique and partially overlapping epitopes on Can f 1. The modification of the identified IgE epitopes provides a pathway for the design of hypoallergens to treat dog allergies.","journal":"Protein Science","year":2025,"id":546179,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1255818,"name":"Alyssa Ball","orcid":"0009-0008-3220-3706","position":1,"is_corresponding":false},{"id":497724,"name":"Jill Glesner","orcid":"0009-0004-0258-4529","position":2,"is_corresponding":false},{"id":1098572,"name":"C. P. LINN","orcid":"0009-0007-9459-1786","position":3,"is_corresponding":false},{"id":875697,"name":"Lisa D. Vailes","orcid":null,"position":4,"is_corresponding":false},{"id":875698,"name":"Sabina Wünschmann","orcid":null,"position":5,"is_corresponding":false},{"id":110872,"name":"Scott A. Gabel","orcid":null,"position":6,"is_corresponding":false},{"id":496261,"name":"Jian Zhang","orcid":"0000-0002-0790-4462","position":7,"is_corresponding":false},{"id":290007,"name":"R. Stokes Peebles","orcid":"0000-0002-1429-7875","position":8,"is_corresponding":false},{"id":378347,"name":"Tomasz Borowski","orcid":"0000-0002-3450-3576","position":9,"is_corresponding":false},{"id":334365,"name":"Geoffrey A. Mueller","orcid":"0000-0001-8361-5323","position":10,"is_corresponding":false},{"id":468127,"name":"Martin D. Chapman","orcid":"0000-0002-0845-3632","position":11,"is_corresponding":false},{"id":497727,"name":"Scott A. Smith","orcid":"0000-0001-5153-2726","position":12,"is_corresponding":false},{"id":310426,"name":"Anna Pomés","orcid":"0000-0002-8729-1829","position":13,"is_corresponding":false},{"id":334366,"name":"M. Chruszcz","orcid":"0000-0001-7521-5485","position":14,"is_corresponding":false},{"id":875081,"name":"Kriti Khatri","orcid":"0000-0002-4757-2677","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:53:32.285899Z","pmid":"40828364","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}