{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:17:27Z","timestamp":1787563047616,"version":"build-2736575974"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI125189-04 , NO1-AI70022"],"award-info":[{"award-number":["R01 AI125189-04 , NO1-AI70022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["2016103"],"award-info":[{"award-number":["2016103"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1109001"],"award-info":[{"award-number":["OPP1109001"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium bovis<\/jats:italic>\n                    bacille Calmette-Gu\u00e9rin (BCG) has been used for 100 years and prevents disseminated tuberculosis and death in young children. However, it shows only partial efficacy against pulmonary tuberculosis (TB) in adults, so new vaccines are urgently needed. The protective efficacy of BCG depends on T cells, which are typically activated by pathogen-derived protein antigens that bind to highly polymorphic major histocompatibility complex (MHC) molecules. Some T cells recognize non-protein antigens\n                    <jats:italic>via<\/jats:italic>\n                    antigen presenting systems that are independent of genetic background, leading to their designation as donor-unrestricted T (DURT) cells. Whether live whole cell vaccines, like BCG, can induce durable expansions of DURT cells in humans is not known. We used combinatorial tetramer staining, multi-parameter flow cytometry, and immunosequencing to comprehensively characterize the effect of BCG on activation and expansion of DURT cell subsets. We examined peripheral blood mononuclear cells (PBMC) derived from a Phase I study of South African adults in which samples were archived at baseline, 3 weeks, and 52 weeks post-BCG revaccination. We did not observe a change in the frequency of total mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, germline encoded mycolyl-reactive (GEM) T cells, or \u03b3\u03b4 T cells at 52 weeks post-BCG. However, immunosequencing revealed a set of TCR-\u03b4 clonotypes that were expanded at 52 weeks post-BCG revaccination. These expanded clones expressed the V\u03b42 gene segment and could be further defined on the basis of biochemical similarity into several \u2018meta-clonotypes\u2019 that likely recognize similar epitopes. Our data reveal that BCG vaccination leads to durable expansion of DURT cell clonotypes despite a limited effect on total circulating frequencies in the blood and have implications for defining the immunogenicity of candidate whole cell TB vaccines.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.834757","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T06:28:46Z","timestamp":1648621726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Durable Expansion of TCR-\u03b4 Meta-Clonotypes After BCG Revaccination in Humans"],"prefix":"10.3389","volume":"13","author":[{"given":"Charlotte A.","family":"James","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle K. 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