{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:08:54Z","timestamp":1779469734984,"version":"3.53.1"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["865175"],"award-info":[{"award-number":["865175"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peptide-based therapeutic vaccines exploit cross-presentation by dendritic cells for the induction of effective T cell responses. Their clinical success, however, has been limited due to incomplete understanding of antigen processing and presentation (APP). Bioorthogonal chemistry (BOC) uses chemical \u201cclick\u201d reactions that can be performed selectively without interference of the cellular environment. A \u201cclick handle\u201d can be incorporated into a biomolecule with only minor effects on its characteristics, allowing selective visualization and tracking of the biomolecule. We generated 10 analogues of the HLA-A2-restricted, immunogenic hepatitis B virus-derived epitope HBcAg18-27 by replacing each amino acid with the click handle homopropargylglycine. Each analogue was tested for (1) peptide binding affinity to HLA-A2, (2) preservation of immunogenicity, and (3) accessibility for on-cell click reactions. Lastly, we performed a proof-of-concept experiment in which we demonstrate the feasibility of BOC for APP studies. All amino acids could be modified with the click handle without loss of HLA binding. Furthermore, 7 out of 10 analogues retained cognate T cell recognition. Two of the most promising analogues were tested and demonstrated to be accessible for on-cell click as well as suitable for long peptide processing and presentation studies. To our knowledge, we are the first to show the feasibility of BOC to study APP in the human setting. With BOC techniques, we may now be able to sensitively follow antigen routing by visualizing the intracellular location of (long) peptides. Furthermore, this tool enables direct and quantitative epitope studies in a T cell-independent manner.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf312","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T05:02:45Z","timestamp":1763701365000},"source":"Crossref","is-referenced-by-count":0,"title":["Bioorthogonal click chemistry to visualize an immunogenic HLA-A2-restricted hepatitis B virus epitope in human monocyte-derived dendritic cells"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6338-2622","authenticated-orcid":false,"given":"Thijmen P","family":"Mostert","sequence":"first","affiliation":[{"name":"Department of Chemical Biology & Immunology, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-6889","authenticated-orcid":false,"given":"Amy L","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam , Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbie J","family":"Luijten","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam , Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-9402","authenticated-orcid":false,"given":"Ward","family":"Doelman","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology & Immunology, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein M E","family":"Isendoorn","sequence":"additional","affiliation":[{"name":"Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri V","family":"Filippov","sequence":"additional","affiliation":[{"name":"Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3733-818X","authenticated-orcid":false,"given":"Sander I","family":"van Kasteren","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology & Immunology, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]},{"name":"Institute of Chemical Immunology, Leiden Institute of Chemistry, Leiden University , Leiden, 2333 CC,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-8315","authenticated-orcid":false,"given":"Sonja I","family":"Buschow","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam , Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2026052212175117800_vkaf312-B1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nri3084","article-title":"Towards a systems understanding of MHC class I and MHC class II antigen presentation","volume":"11","author":"Neefjes","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"2026052212175117800_vkaf312-B2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","volume":"22","author":"Pishesha","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"2026052212175117800_vkaf312-B3","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.it.2016.08.010","article-title":"Present yourself! 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