{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:32:20Z","timestamp":1793064740177,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011033","name":"Thermo Fisher Scientific","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Identifying HLA amino acid residues that account for an observed specificity (reactivity profile) is critical for serological categorisation at the B\u2010cell epitope level. Human monoclonal antibody, LB_DQB0402_A, produced by an individual typed\n                    <jats:italic>DQA1*03:03<\/jats:italic>\n                    ,\n                    <jats:italic>DQA1*05:05\/*05:11<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*03:01<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*03:01<\/jats:italic>\n                    against an immuniser typed\n                    <jats:italic>DQA1*01:02<\/jats:italic>\n                    ,\n                    <jats:italic>DQA1*05:05<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*03:01<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*06:02<\/jats:italic>\n                    , reacts strongly to\n                    <jats:italic>DQB1*04\/05\/06<\/jats:italic>\n                    single antigen beads (SABs), for which 55R, present in\n                    <jats:italic>DQB1*04\/05\/06<\/jats:italic>\n                    alleles, has been previously proposed to be the target eplet. In this study, the antibody was also observed to react with\n                    <jats:italic>DQB1*03<\/jats:italic>\n                    SABs albeit with reduced intensities and only at antibody concentrations higher than 1\u2009\u03bcg\/mL. Additional weak reactivities to\n                    <jats:italic>DQB1*02<\/jats:italic>\n                    SABs were also observed when the concentration was further increased to 10\u2009\u03bcg\/mL. Different clusters responsible for the three concentration\u2010dependent reactivity profiles were predicted by AminoAcid3D algorithm, and two (DQB1_46V and DQB1_55R) were verified using engineered variants (EVs) derived from\n                    <jats:italic>DQA1*02:01<\/jats:italic>\n                    \u2010\n                    <jats:italic>DQB1*06:01<\/jats:italic>\n                    expressed on cells and immobilised on beads, with bead assay more sensitive than cell assay. However, EVs targeting the third cluster (DQB1_81H) did not impact binding, suggesting 81H is not involved in binding to\n                    <jats:italic>DQB1*04\/05\/06<\/jats:italic>\n                    when strong interacting 46V and 55R are present. On the other hand, 81H was predicted to account for the weak interactions with\n                    <jats:italic>DQB1*02<\/jats:italic>\n                    antigens when neither 46V nor 55R are present. As to\n                    <jats:italic>DQB1*03<\/jats:italic>\n                    , only 46V and 81H are present, so the reduced signals could be due to the missing 55R. This antibody appears to pivot toward the stronger interacting residues available on different antigens. Although HLA alloantibodies develop and affinity mature against a specific foreign conformation, reactivity spread is expected if another antigen shares the same essential residue\/region for specificity (ERS) and similar constituents of an epitope. However, this study demonstrates that reactivities in an in\u00a0vitro setting can still occur even to antigens, including self, not carrying the same ERS as the immuniser, albeit of a much weaker intensity only observed above certain high antibody concentrations. While the clinical relevance of such observations remains unknown, this level of differentiation impacts the analysis of antigenicity.\n                  <\/jats:p>","DOI":"10.1111\/tan.70889","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:04:01Z","timestamp":1792641841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concentration\u2010Dependent Reactivity Profiles of a Human Monoclonal Antibody Recognising\n                    <i>HLA\u2010DQB1*04\/05\/06<\/i>\n                    and at Reduced Intensities to\n                    <i>DQB1*03<\/i>\n                    Antigens"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-8756","authenticated-orcid":false,"given":"Tina","family":"Meng","sequence":"first","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4259-9678","authenticated-orcid":false,"given":"Ujjwala","family":"Singh","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3836-9490","authenticated-orcid":false,"given":"Naiiry","family":"Petrosyan","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-7206","authenticated-orcid":false,"given":"Fred","family":"Quiroz","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6486-5988","authenticated-orcid":false,"given":"Xiaoliang","family":"Yao","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1125-323X","authenticated-orcid":false,"given":"Than Than","family":"Han","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-6070","authenticated-orcid":false,"given":"Hsiao\u2010Min","family":"Chang","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-3925","authenticated-orcid":false,"given":"Eric Ka\u2010Wai","family":"Hui","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-6187","authenticated-orcid":false,"given":"David","family":"Suh","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2281-1869","authenticated-orcid":false,"given":"Vincent","family":"Ma","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6043-6219","authenticated-orcid":false,"given":"Elaina","family":"Rybak","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-014X","authenticated-orcid":false,"given":"Quansheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4763-3298","authenticated-orcid":false,"given":"Zhifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Software Engineering, Transplant Diagnostics Thermo Fisher Scientific Inc.  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