{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:41:23Z","timestamp":1785300083626,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T00:00:00Z","timestamp":1516320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA104947 (MIN)"],"award-info":[{"award-number":["R01 CA104947 (MIN)"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 AI129543 (MIN)"],"award-info":[{"award-number":["R01 AI129543 (MIN)"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 CA154778 (MIN)"],"award-info":[{"award-number":["P01 CA154778 (MIN)"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["F30 CA180731 (TTS)"],"award-info":[{"award-number":["F30 CA180731 (TTS)"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T cell receptor (TCR) gene-modified T cells are a promising immunotherapy but require refinement to improve clinical responses and limit off-target toxicities. A variety of TCR and gene-delivery vector modifications have been developed to enhance introduced TCR expression and limit introduced\/endogenous TCR chain mispairing, improving target antigen recognition and minimizing mispairing-induced cross-reactivity. Using our well-characterized HCV1406 TCR, we previously compared the impact of various chain pairing enhancing modifications on TCR expression and cognate antigen recognition. HCV1406 TCR is also natively cross-reactive against naturally occurring altered peptide ligands (APLs), which was shown to be dependent on high TCR surface density. In this report, we observed in a Jurkat model that absent TCR chain pairing competition alleviated CD8-dependent APL recognition and induced novel cross-reactivity of HCV1406 TCR. We then compared chain pairing enhancing modifications\u2019 effects on TCR cross-reactivity in Jurkat and T cells, showing C-terminal leucine zippers and constant region murinization alleviated CD8 dependence and induced novel APL recognition. While modifications enhancing TCR chain pairing intend to avoid cross-reactivity by limiting mispairing with the endogenous TCR, these data suggest they may also enhance natural cross-reactivity and reduce dependence on CD8. These observations have significant implications on the design\/implementation of TCR gene-modified T cells.<\/jats:p>","DOI":"10.1002\/jlb.5a0817-314r","type":"journal-article","created":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T14:52:42Z","timestamp":1516373562000},"page":"973-983","source":"Crossref","is-referenced-by-count":15,"title":["TCR modifications that enhance chain pairing in gene-modified T cells can augment cross-reactivity and alleviate CD8 dependence"],"prefix":"10.1093","volume":"103","author":[{"given":"Timothy T","family":"Spear","sequence":"first","affiliation":[{"name":"Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago , Maywood, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra C","family":"Foley","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago , Maywood, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Garrett-Mayer","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, South Carolina, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina , Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago , Maywood, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,19]]},"reference":[{"key":"2023032405561347500_","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00262-016-1842-5","article-title":"Strategies to genetically engineer T cells for cancer 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