{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:27Z","timestamp":1792785987541,"version":"4.5.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institutes of Health\u2019s Human Immunology","award":["U19 AI118626"],"award-info":[{"award-number":["U19 AI118626"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["75N93024C00057"],"award-info":[{"award-number":["75N93024C00057"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-2038238"],"award-info":[{"award-number":["DGE-2038238"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the TCR repertoire\u2019s diversity and the complexity of TCR-antigen recognition. We developed the peptide-driven identification of TCRs (PDI-TCR) assay that combines in vitro expansion of cells with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. A key feature of PDI-TCR is the ability to distinguish true antigen-specific TCR clonotypes from TCRs associated with unspecific bystander activation by comparing responses to nonoverlapping peptide pools. We applied PDI-TCR to tuberculosis (TB) patients, sampling blood at diagnosis and throughout treatment, and Mycobacterium tuberculosis (Mtb)\u2013sensitized healthy individuals (IGRA+). We identified hundreds of Mtb-specific TCRs, as well as unspecific TCRs, and characterized their phenotype in each cohort by single-cell RNA sequencing ex vivo. Mtb-specific T cells were highly diverse, with short-lived effector phenotypes only present in TB at diagnosis, while memory phenotypes were maintained through treatment. In contrast, unspecific expanded T cells were more clonally restricted, had a cytotoxic phenotype, and were maintained throughout treatment. While the PDI-TCR parameters used in this study are specific to Mtb, the underlying approach is broadly applicable to the study of antigen-specific T cells and can be adapted as needed for other antigen systems. Thus, PDI-TCR is a powerful tool for identifying antigen-specific TCRs and enables direct ex vivo identification and monitoring of antigen-specific T cells.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf287","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T11:04:07Z","timestamp":1763291047000},"source":"Crossref","is-referenced-by-count":3,"title":["Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-8592","authenticated-orcid":false,"given":"Rashmi","family":"Tippalagama","sequence":"first","affiliation":[{"name":"La Jolla Institute for Immunology Center for Vaccine Innovation, , La Jolla, CA 92037,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Trevizani","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology Center for 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Division of Immunology, Department of Pathology, , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology Center for Vaccine Innovation, , La Jolla, CA 92037,","place":["United States"]},{"name":"University of California San Diego Department of Medicine, , La Jolla, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Lindestam Arlehamn","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology Center for Vaccine Innovation, , La Jolla, CA 92037,","place":["United States"]},{"name":"Statens Serum Institut Center for Vaccine Research, Department of Infectious Disease Immunology, , 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