{"id":48869,"date":"2025-11-16T19:24:47","date_gmt":"2025-11-16T18:24:47","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/peptide-driven-identification-of-tcrs-reveals-dynamics-and-phenotypes-of-cd4-t-cells-in-tuberculosis\/"},"modified":"2025-11-16T19:24:47","modified_gmt":"2025-11-16T18:24:47","slug":"peptide-driven-identification-of-tcrs-reveals-dynamics-and-phenotypes-of-cd4-t-cells-in-tuberculosis","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/peptide-driven-identification-of-tcrs-reveals-dynamics-and-phenotypes-of-cd4-t-cells-in-tuberculosis\/","title":{"rendered":"Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Nov 16:vkaf287. doi: 10.1093\/jimmun\/vkaf287. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the TCR repertoire&#8217;s 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)-sensitized 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.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41241821\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251116132446&amp;v=2.18.0.post22+67771e2\">41241821<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf287\">10.1093\/jimmun\/vkaf287<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Nov 16:vkaf287. doi: 10.1093\/jimmun\/vkaf287. Online ahead of print. ABSTRACT Assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the TCR repertoire&#8217;s 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 &#8230; <a title=\"Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/11\/16\/peptide-driven-identification-of-tcrs-reveals-dynamics-and-phenotypes-of-cd4-t-cells-in-tuberculosis\/\" aria-label=\"Read more about Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-48869","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48869","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=48869"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/48869\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=48869"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=48869"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=48869"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}