{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:01:56Z","timestamp":1790154116958,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000923","name":"Silicon Valley Community Foundation","doi-asserted-by":"publisher","award":["2023\u2010332384"],"award-info":[{"award-number":["2023\u2010332384"]}],"id":[{"id":"10.13039\/100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["EXPERT\u2010J"],"award-info":[{"award-number":["EXPERT\u2010J"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>T\u2010cell receptor repertoires are commonly characterized through sequence diversity and antigen binding, while the cellular functions associated with individual receptors are often measured separately. In this review, I consider how functional information can be incorporated more directly into repertoire analysis by linking receptor identity with measurable effector outputs at single\u2010cell resolution. I focus on Nanovial\u2010based technologies that combine antigen\u2010specific capture, stimulation, secretion measurement, viable\u2010cell recovery, and downstream sequencing in workflows compatible with flow cytometry and single\u2010cell sequencing platforms. Studies using conventional peptide\u2013major histocompatibility complex ligands, the non\u2010classical antigen\u2010presenting molecules MR1 and CD1d, and secretion\u2010encoded single\u2010cell sequencing illustrate how these approaches can complement binding\u2010based enrichment by adding information about secretory effector responses. I also discuss the extension of this framework from ligand\u2010defined screening to dyad\u2010resolved assays involving target cells, which can reveal how receptor identity relates to transcriptional and functional programs arising during direct cell\u2013cell interactions. Together, these developments provide tools for studying relationships among TCR sequence, antigen recognition, and cellular response, with potential applications in therapeutic receptor discovery and in generating datasets for predictive models of T\u2010cell function.<\/jats:p>","DOI":"10.1111\/imr.70171","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:32:05Z","timestamp":1789014725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining Functional T Cell Receptor Repertoires With Nanovial\u2010Based Screening"],"prefix":"10.1111","volume":"342","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-4284","authenticated-orcid":false,"given":"Dino","family":"Di Carlo","sequence":"first","affiliation":[{"name":"Department of Bioengineering, California NanoSystems Institute, Jonsson Comprehensive Cancer Center University of California  Los Angeles California USA"},{"name":"EXPERT\u2010GRI Office and Graduate School of Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00823-w"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf3700"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.036"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2020.07.010"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-4494-1_3"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01378"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700242"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0276294"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202451666"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2320442121"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c22721"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iotech.2025.101076"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2021.0052"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15030384"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuno.2022.100009"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx3162"},{"issue":"3","key":"e_1_2_12_18_1","article-title":"T\u2010Cell Activation\u2010Induced Marker Assays in Health and Disease","volume":"54","author":"Poloni C.","year":"2024","journal-title":"European Journal of Immunology"},{"issue":"4","key":"e_1_2_12_19_1","article-title":"Droplet\u2010Based mRNA Sequencing of Fixed and Permeabilized Cells by CLInt\u2010Seq Enables Antigen\u2010Specific TCR Cloning","volume":"118","author":"Nesterenko P. A.","year":"2021","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_20_1","article-title":"Single\u2010Cell RNA Sequencing Coupled to TCR Profiling of Large Granular Lymphocyte Leukemia","volume":"13","author":"Gao S.","year":"2022","journal-title":"Nature Communications"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41378-022-00422-x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c11420"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.slast.2021.10.004"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c05857"},{"issue":"1","key":"e_1_2_12_25_1","first-page":"9180","article-title":"Enhancing Large Particle Recovery in High\u2010Throughput Flow Cytometry by Reducing Break\u2010Off Point Interference","volume":"15","author":"Sakamoto N.","year":"2025","journal-title":"Scientific Reports"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c19139"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.02.662376"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c18391"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.64898\/2026.02.05.704136"},{"issue":"5","key":"e_1_2_12_30_1","first-page":"1584","article-title":"Linking Single\u2010Cell Transcriptomes With Secretion Using Secretion\u2010Encoded Single\u2010Cell Sequencing (SEC\u2010Seq)","volume":"20","author":"Langerman J.","year":"2025","journal-title":"Nature Protocols"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-026-03177-2"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.70171","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imr.70171","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.70171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:10:07Z","timestamp":1790151007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imr.70171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/imr.70171"],"URL":"https:\/\/doi.org\/10.1111\/imr.70171","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"value":"0105-2896","type":"print"},{"value":"1600-065X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70171"}}