{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:32:23Z","timestamp":1793064743274,"version":"4.5.0"},"reference-count":18,"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 B\u2010cell epitope level. Human monoclonal antibody, LB_DQB0501_C (hIgG1l), produced by an individual typed\n                    <jats:italic>DQA1*01:02<\/jats:italic>\n                    ,\n                    <jats:italic>DQA1*03:01<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*03:02<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*06:09<\/jats:italic>\n                    against an immuniser typed\n                    <jats:italic>DQA1*01:01<\/jats:italic>\n                    ,\n                    <jats:italic>DQA1*01:02<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*05:01<\/jats:italic>\n                    ,\n                    <jats:italic>DQB1*06:09<\/jats:italic>\n                    , reacts strongly to many but not all\n                    <jats:italic>DQB1*02<\/jats:italic>\n                    ,\n                    <jats:italic>*03<\/jats:italic>\n                    ,\n                    <jats:italic>*05<\/jats:italic>\n                    and\n                    <jats:italic>*06<\/jats:italic>\n                    single antigen beads. Within each first\u2010field molecular typing group, some beads were recognised weakly by the antibody or not at all even at 10\u2009\u03bcg\/mL. Only one prediction (DQB1_130R185T as a pair) was made using AminoAcid3D (AA3D), an algorithm that defines each HLA molecule as a series of overlapping 3\u2010dimensional clusters and deduces the potential essential region that could account for an observed reactivity profile. Among various scenarios, DQB1_130R185T was predicted only when the weak signals (TMFI about 1000) were included as positive. Both 130R and 185T, about 10\u2009\u00c5 apart, were confirmed as essential for binding using engineered variants as the change of either led to complete loss of binding in both cell and bead assays. Additional residues in the vicinity were also tested for their relative contributions. Besides polymorphic residues in DQB1 at positions 135 or likely 182 that could explain the signal differences within each\n                    <jats:italic>DQB1*02<\/jats:italic>\n                    or\n                    <jats:italic>DQB1*05<\/jats:italic>\n                    group, three conserved residues (DQB1_132F, _174H and _183P) were also shown to be critical in securing the binding, indicating multiple residues including conserved are needed to maintain a stable interaction. Epitopes distal to the peptide\u2010binding domains have not been sufficiently described by the conventional serological typing. Even using HLAMatchmaker, 130R185T was not predicted despite both 130R (verified, level A2) and 185T (unverified) are listed separately as an HLA\u2010DQ eplet in HLA Eplet Registry. This study provides evidence that AA3D is a useful research tool for epitope analysis. Once a predicted specificity determinant is experimentally verified, both polymorphic and conserved positions nearby should be further investigated for their contributions to the epitope. Such knowledge could become the basis of the ongoing efforts in serological categorisation.\n                  <\/jats:p>","DOI":"10.1111\/tan.70835","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:52:38Z","timestamp":1792641158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Amino Acid Residues, Distal to the Peptide\u2010Binding Domain, That Confer Serological Distinctions Within Each\n                    <i>HLA\u2010DQB1*02<\/i>\n                    ,\n                    <i>*03<\/i>\n                    ,\n                    <i>*05<\/i>\n                    and\n                    <i>*06<\/i>\n                    Antigen Group"],"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.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5472-909X","authenticated-orcid":false,"given":"James","family":"Jones","sequence":"additional","affiliation":[{"name":"Customer Experience, Transplant Diagnostics Thermo Fisher Scientific Inc.  West Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-1193","authenticated-orcid":false,"given":"Dave","family":"Roelen","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-2336","authenticated-orcid":false,"given":"Cynthia S. M.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-188X","authenticated-orcid":false,"given":"Sebastiaan","family":"Heidt","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Internal Medicine Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9810-2344","authenticated-orcid":false,"given":"Dave","family":"Lowe","sequence":"additional","affiliation":[{"name":"Research and Development, Transplant Diagnostics Thermo Fisher Scientific Inc.  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