{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:25:14Z","timestamp":1793305514886,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Patients with acute myeloid leukemia (AML) often carry the same gene mutations. Neoantigens encoded by these mutations are attractive targets for immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched for public human leukocyte antigen (HLA) class II-restricted neoantigens on AML using an <jats:italic>in vitro<\/jats:italic> T cell stimulation method. Peptides from 26 recurrent genetic aberrations were assessed for predicted HLA class II binding, and 24 long neopeptides encoded by 10 recurrent mutations were synthesized. Naive CD4 T cells from healthy individuals were cocultured with autologous dendritic cells pulsed with neopeptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multiple CD4 T cell clones were isolated that recognized neopeptides encoded by 5 different genetic aberrations. Two of these peptides, one from the well-known <jats:italic>DNMT3A-R882H<\/jats:italic> hotspot mutation and one from a long alternative reading frame created by frameshift mutations in <jats:italic>RUNX1<\/jats:italic>, were recognized by CD4 T cell clones after endogenous processing and presentation on cell lines transduced or CRISPR-Cas9-edited with the mutation of interest. The T cell clone for DNMT3A-R882H was also activated upon stimulation with primary AML samples from HLA-DQB1*06:02 or -DQB1*06:03 positive patients with the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We here identified a public HLA class II-restricted neoantigen encoded by a driver mutation occurring in 10% of patients with AML that could become an important target for immunotherapy to treat patients with <jats:italic>DNMT3A-R882H<\/jats:italic>-mutated AML.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1556121","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T09:15:01Z","timestamp":1741857301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Mutated DNMT3A creates a public HLADQ- binding neoantigen on acute myeloid leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Dyantha I.","family":"van der Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Argiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan N. 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