{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:19:15Z","timestamp":1792808355731,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Immunology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["CGCATF-2023\/100003"],"award-info":[{"award-number":["CGCATF-2023\/100003"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CGCATF-2025\/100002"],"award-info":[{"award-number":["CGCATF-2025\/100002"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["OT2CA297206"],"award-info":[{"award-number":["OT2CA297206"]}]},{"id":[{"id":"https:\/\/ror.org\/00v7th354","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Cancer Research Institute and KiKa","id":[{"id":"https:\/\/ror.org\/02f3xk561","id-type":"ROR","asserted-by":"crossref"}]},{"name":"EMBO","award":["ALTF 643-2025"],"award-info":[{"award-number":["ALTF 643-2025"]}],"id":[{"id":"https:\/\/ror.org\/04wfr2810","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Louis Jeantet prize and Stevin Award"},{"name":"Marie Sklodowska Curie Actions","award":["101208803"],"award-info":[{"award-number":["101208803"]}]},{"id":[{"id":"https:\/\/ror.org\/041evnj42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Tumors contain a mixture of T cells with bystander reactivities and reactivities towards different, frequently patient-specific, cancer (neo)antigens. The one-step identification of highly active TCR\u2013antigen pairs in human tumors would be valuable, both as a monitoring tool and to boost T cell reactivities of interest. Here, we develop PAIR-Scan, an HLA-agnostic library-on-library screening technology that identifies functionally active TCR\u2013neoantigen pairs among tens of thousands of candidate pairs in a single step. We demonstrate the value of PAIR-Scan on a range of tumor samples and for the direct identification of TCR-recognized minimal peptides. In addition, we demonstrate that PAIR-Scan correctly ranks TCRs reactive to the same antigen by their relative tumor-killing efficiency. Together, these data demonstrate the value of PAIR-Scan for both the dissection of T cell responses in clinical samples and to generate large-scale datasets for the development of predictive models of TCR reactivity.<\/jats:p>","DOI":"10.64898\/2026.09.07.749948","type":"posted-content","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:15:20Z","timestamp":1789406120000},"source":"Crossref","is-referenced-by-count":0,"title":["PAIR-Scan: Single-step identification of highly potent TCR\u2013neoantigen pairs through library-on-library screening"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7179-0594","authenticated-orcid":false,"given":"Marius","family":"Messemaker","sequence":"first","affiliation":[{"name":"Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands"},{"name":"Oncode Institute, Utrecht, The 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