{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T11:37:03Z","timestamp":1793101023566,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92469302"],"award-info":[{"award-number":["92469302"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82025022"],"award-info":[{"award-number":["82025022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2306400"],"award-info":[{"award-number":["2023YFC2306400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["ZDSYS20210623091810030"],"award-info":[{"award-number":["ZDSYS20210623091810030"]}]},{"name":"Shenzhen Science and Technology Program","award":["KQTD20200909113758004"],"award-info":[{"award-number":["KQTD20200909113758004"]}]},{"name":"R&D Program of Guangzhou Laboratory","award":["SRPG22-006"],"award-info":[{"award-number":["SRPG22-006"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shenzhen Clinical Research Center for Tuberculosis","award":["20210617141509001"],"award-info":[{"award-number":["20210617141509001"]}]},{"name":"Science and Technology Innovation Committee of Shenzhen Municipality","award":["JCYJ20200109144201725"],"award-info":[{"award-number":["JCYJ20200109144201725"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M762144"],"award-info":[{"award-number":["2024M762144"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003785","name":"Medical Scientific Research Foundation of Guangdong Province of China","doi-asserted-by":"publisher","award":["B2026312"],"award-info":[{"award-number":["B2026312"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Reliable structural prediction of T-cell receptors (TCRs) is essential for dissecting antigen recognition and accelerating TCR-based therapeutic development, yet the performance of emerging computational structure prediction models for this task requires further systematic evaluation under practical usage conditions. Here, we assembled a manually curated dataset of TCR crystal structures and compared five state-of-the-art predictors\u2014AlphaFold2 (v2.3.1), TCRmodel2, AlphaFold3, ESMFold, and tFold-TCR\u2014in both single-chain and paired-chain modes. Using pLDDT and model confidence scores (pTM\/ipTM), we defined optimized quality thresholds for assessing model reliability. Our analyses revealed a pronounced context dependence in model performance: AlphaFold3 achieved the highest accuracy for paired-chain TCR predictions (excluding the \u03b1-FRs domain), while tFold-TCR excelled in single-chain modeling (excluding V\u03b1, CDR1\u03b1, CDR1\u03b2, and CDR2\u03b2 domains), indicating that their performance varies significantly depending on the prediction mode and specific structural domains. We further showed that, under our evaluation conditions, structure-guided clustering of predicted CDR3\u03b2 loops showed improved sensitivity and achieved higher conformational consistency for certain antigen-specific TCR groups compared with conventional sequence-based methods. Applying this framework, we successfully identified two functional SARS-CoV-2\u2013specific TCRs using a TPS (TPSGTWLTY)-reactive TCR template. Our study establishes a practical comparative framework and highlights the translational potential of structure-guided computational workflows for antigen-specific TCR discovery.<\/jats:p>","DOI":"10.1093\/bib\/bbag382","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:44:39Z","timestamp":1784231079000},"source":"Crossref","is-referenced-by-count":0,"title":["A comparative and exploratory analysis of computational methods for TCR structural prediction and antigen-specific TCR discovery"],"prefix":"10.1093","volume":"27","author":[{"given":"Qiang","family":"Huang","sequence":"first","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyin","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JuanJuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-1389","authenticated-orcid":false,"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Department of Biochemistry, School of Medicine, Southern University of Science and Technology , No. 29 Bulan Road, Longgang District, Shenzhen 518112, Guangdong Province ,","place":["China"]},{"name":"Institute of Human Immunology, Shenzhen Medical Academy of Research and Translation (SMART) , 17F, Tower A, Guangming Life Science Park, Xinhu Subdistrict, Guangming District, Shenzhen 518107 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