{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:11:52Z","timestamp":1793481112048,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"La Jolla Institute for Immunology under National Institutes of Health","doi-asserted-by":"publisher","award":["75N93019C00066"],"award-info":[{"award-number":["75N93019C00066"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Infection with Bordetella pertussis causes whooping cough. CD4+ T cell responses depend on bacterial peptides displayed by HLA class II, yet allele- and strain-resolved maps of naturally processed B. pertussis HLA-DR ligands remain limited. We sought to define which antigens yield HLA-DR ligands in a human macrophage model and whether presentation is skewed by HLA-DR molecule and bacterial strain. Methods: THP-1\u2013derived macrophages were pulsed with whole-cell lysates of B. pertussis vaccine\/reference strain Tohama I or clinical isolate D420. HLA-DR was immunoaffinity purified; eluted peptides were identified by LC-MS\/MS and assigned to HLA-DR molecules encoded by HLA-DRB1*01:01, HLA-DRB1*15:01, and HLA-DRB5*01:01. Results: We identified 63 B. pertussis peptide ligands from 29 source proteins. Presentation was skewed by HLA-DR molecule: DRB1*01:01 accounted for 37 ligands from 21 antigens, DRB1*15:01 for 22 from 7, and DRB5*01:01 for 4 from 4. Most source proteins contributed ligands primarily to one HLA-DR molecule, so an antigen that supplies peptides to one DR product need not supply peptides to another. Strain further partitioned the ligandome: 32 ligands unique to Tohama I, 12 to D420, and only 19 from 8 proteins with both lysates. Only three antigens contributed ligands to both DRB1*01:01 and DRB1*15:01; two of these, pertactin and filamentous hemagglutinin, are components of current acellular pertussis vaccines. Conclusions: B. pertussis HLA-DR ligandomes are jointly shaped by bacterial strain and HLA-DR molecule. Antigens can interact selectively with individual HLA-DR products, and peptides from a given antigen may be recovered after pulse with one strain but not another. These findings support HLA-DR and strain-aware interpretation of class II presentation and nominate BrkA autotransporter (Bordetella resistance to killing A), outer membrane protein A (OmpA), tracheal colonization factor (TcfA), and a divalent metal transporter (DMT) family transporter for follow-up.<\/jats:p>","DOI":"10.3390\/vaccines14090733","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:00:48Z","timestamp":1787644848000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Allele-Skewed HLA-DR Immunopeptidomes of Bordetella pertussis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8285-7985","authenticated-orcid":false,"given":"Hooman","family":"Yari","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-8703","authenticated-orcid":false,"given":"Saghar","family":"Kaabinejadian","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-5272","authenticated-orcid":false,"given":"Ricardo","family":"da Silva Antunes","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra K.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2250","authenticated-orcid":false,"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA"},{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41467-024-46560-w","article-title":"Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis","volume":"15","author":"Gillard","year":"2024","journal-title":"Nat. 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