{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:46:20Z","timestamp":1784810780941,"version":"3.55.0"},"reference-count":100,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI135817"],"award-info":[{"award-number":["U19 AI135817"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The IgE\u2010mediated CD4 T\u2010cell response to peanut (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Arachis hypogaea<\/jats:italic>\n                      <\/jats:styled-content>\n                      ) is heterogeneous, yet TH2 cells remain central drivers of pathology. This study aimed to dissect this complexity at the epitope level by focusing on the HLA\u2010DRB1*15:01\u2013DRB5*01:01 haplotype. Specifically, we examined how distinct epitope\u2010specific T\u2010cell subsets shape the immunological landscape of peanut allergy in peanut\u2010allergic (PA) versus non\u2010peanut\u2010allergic (NPA) individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using in\u00a0vitro and ex\u00a0vivo MHC\u2010II tetramer approaches, the phenotype, frequency, function, and transcriptome of CD4 T\u2010cell responses to novel Ara h epitopes were assessed. Bulk RNA sequencing further characterised these T cells, allowing identification of subsets associated with TH2 polarisation in PA individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven HLA\u2010DRB1*15:01 and DRB5*01:01\u2010restricted epitopes were identified in Ara h 1, 2, 3, 6, 7, and 8 using tetramer\u2010guided epitope mapping on cell lines, followed by ex\u00a0vivo validation in peripheral blood. T\u2010cell phenotype was epitope\u2010dependent, with a distinct TH2A population specific to the epitope Ara h 2\n                      <jats:sub>105\u2013124<\/jats:sub>\n                      (Ara h 2 p14) detected only in PA donors. These TH2A cells were phenotypically and transcriptionally distinct, marked by high CRTH2\/CD161, low CD27, IL\u20105 production, and gene enrichment in cytokine signalling and lipid metabolism. Other epitope\u2010specific T\u2010cell subsets displayed more heterogeneous gene profiles related to immune activation, differentiation, and antigen presentation, underscoring the complexity of peanut\u2010specific responses even within a single HLA haplotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reveal that the strong TH2 bias in DRB1*15:01\u2010DRB5*01:01 PA individuals arises from a distinct subset of Ara h 2 p14\u2010specific TH2A cells characterised by a specialised metabolic and cytokine signalling program. At the same time, the functional diversity observed in non\u2010Ara h 2 p14 subsets highlights the potential for leveraging these populations in tolerance\u2010promoting therapies. Understanding the epitope\u2010level heterogeneity of peanut\u2010specific T\u2010cells provides insight into the epitope\u2010specific mechanisms driving peanut allergy and has potential implications for therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cea.70072","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T01:23:49Z","timestamp":1746062629000},"page":"820-833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ara h 2\n                    <sub>105\u2010124<\/sub>\n                    \u2010Specific TH2A Cells Drive Peanut Allergy in DRB1*15:01 Individuals: A Detailed Epitope Analysis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-5686","authenticated-orcid":false,"given":"Rebecca A.","family":"Gomez","sequence":"first","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-8365","authenticated-orcid":false,"given":"Jue","family":"Hou","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"},{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-9926","authenticated-orcid":false,"given":"Vivian H.","family":"Gersuk","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-8157","authenticated-orcid":false,"given":"I\u2010Ting","family":"Chow","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"},{"name":"Immune Medicine Division Adaptive Biotechnologies  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-830X","authenticated-orcid":false,"given":"Mary L.","family":"Farrington","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Virginia Mason Franciscan Health  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7365-510X","authenticated-orcid":false,"given":"David","family":"Robinson","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Virginia Mason Franciscan Health  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-4599","authenticated-orcid":false,"given":"William W.","family":"Kwok","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"},{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14666"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2015.36.3819"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.12.622"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12429"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e3283464cf0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.04.005"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(91)90325-I"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(92)90469-I"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5349"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf4022509"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02334.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.09.010"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051728"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.1998.00168.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20106749(94)90237\u20102"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.09.011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.1033"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.146.12.4055"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830221016"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam9171"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15966"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.07.023"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15276"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.03.020"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204620"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01408"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.02.028"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.2009.03431.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.11.6665"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8476"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt005"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.09.014"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.03.037"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aax8767"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-218-6_40"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12324"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-3-r25"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00984"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2972::AID-IMMU2972>3.0.CO;2-#"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.6.2417"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.139.5.1589"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.025"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.10.035"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00332-1"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3730"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.136.7.2348"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.2.279"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.142.2.679"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.10-OA-0230"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804146200"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20102952(81)90265\u20103"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1238"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.12.005"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1683"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7310002"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.10.1837"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.019"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00243-6"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.977394"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01949"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12787"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.06.007"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.09.009"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13683"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800269-JLR200"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12521"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/44385"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048603"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102764"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00038"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/22572"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2855"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1159\/000097357"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.3.1332"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.014"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003613"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.066"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065672"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071714-034355"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151159"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0976"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxae031"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02186.x"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/1710-1492-10-27"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.07.014"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm290"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609501200"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502643"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260204"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.144.2.548"},{"key":"e_1_2_10_99_1","first-page":"550","article-title":"Regulatory Roles of IL\u201012, IL\u20104 and IFN\u2010Gamma on IgE Synthesis in Atopic Patients","volume":"112","author":"Liu M.","year":"1999","journal-title":"Chinese Medical Journal"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.033"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf098"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.70072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T09:22:07Z","timestamp":1764148927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.70072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":100,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/cea.70072"],"URL":"https:\/\/doi.org\/10.1111\/cea.70072","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"assertion":[{"value":"2024-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}