{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:24:07Z","timestamp":1787747047632,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["VI.Vidi.194.084"],"award-info":[{"award-number":["VI.Vidi.194.084"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10710062310009"],"award-info":[{"award-number":["10710062310009"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Shape space<\/jats:italic>\n                    is a decades\u2010old conceptual model of antibody\u2013antigen interactions that underlies antigenic maps used to trace viral evolution. Here, we apply this concept to T cell receptors (TCRs) and the peptide\u2013MHC complexes (pMHCs) that they recognize. We start by reviewing the history of shape space and its deep connections to concepts in statistical physics (energy landscapes) and computer science (complexity theory). Leveraging these connections, we propose a model in which TCR\u2010pMHC binding relies on multiple, possibly conflicting, structural constraints\u2014implying that pMHCs recognized by the same TCR occupy several disjoint, non\u2010convex regions in shape space. Our model makes two central predictions: (1) even small pMHC structure alterations can have major effects on immunogenicity; (2) two pMHCs recognized by the same TCR can have very different structures. We show that published TCR\u2010pMHC interaction data generated by mutagenesis assays lend some support for this idea. We conclude by discussing implications of a multispecific and non\u2010convex T cell epitope shape space for the prediction of immune responses in cancer immunotherapy and other applications.\n                  <\/jats:p>","DOI":"10.1111\/imr.70152","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:15:48Z","timestamp":1786108548000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["What Does the Shape Space of T Cell Epitopes Look Like?"],"prefix":"10.1111","volume":"341","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0626-9540","authenticated-orcid":false,"given":"Franka","family":"Buytenhuijs","sequence":"first","affiliation":[{"name":"Data Science, Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-3237","authenticated-orcid":false,"given":"Gijs","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Data Science, Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-9458","authenticated-orcid":false,"given":"Johannes","family":"Textor","sequence":"additional","affiliation":[{"name":"Data Science, Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"},{"name":"Medical Biosciences Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.169.3950.1042"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030690"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20105193(79)90275\u20103"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105193(05)80601\u20100"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.1997.0495"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.2001.2347"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097211"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2018.03.022"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physchem\u2010050317\u2010021219"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0033583526100134"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340210302"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2016.1235966"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.04.010"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2024.100634"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abq4450"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.17.633534"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1109\/RISP.1994.296580"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1145\/262793.262811"},{"key":"e_1_2_14_20_1","first-page":"1289","volume-title":"Proceedings of the 1st Annual Conference on Genetic and Evolutionary Computation\u2010Volume 2. 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