{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:32:52Z","timestamp":1787239972582,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n \n Tuberculosis (TB) caused by\n Mycobacterium tuberculosis<\/jats:italic>\n (Mtb) infection is a serious threat to human health. Vaccination with BCG prevents the development of the most severe forms of TB disease in infants and was recently shown to prevent Mtb infection in previously uninfected adolescents. \u03b3\u03b4 T cells play a major role in host defense at mucosal sites and are known to respond robustly to mycobacterial infection. However, our understanding of the effects of BCG vaccination on \u03b3\u03b4 T cell responses is incomplete.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this study we performed \u03b3\u03b4 T cell receptor (TCR) repertoire sequencing of samples provided pre- and post-BCG vaccination from 10 individuals to identify specific receptors and TCR clones that are induced by BCG.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, there was no change in the diversity of \u03b3TCR or \u03b4TCR clonotypes in post- vs pre-BCG samples. Furthermore, the frequencies of TCR variable and joining region genes were minimally modulated by BCG vaccination at either the \u03b3TCR or \u03b4TCR loci. However, the \u03b3TCR and \u03b4TCR repertoires of individuals were highly dynamic; a median of ~1% of \u03b3TCR and ~6% of \u03b4TCR in the repertoire were found to significantly expand or contract in post- vs pre-BCG comparisons (FDR-q &lt; 0.05). While many of the clonotypes whose frequency changed after BCG vaccination were not shared among multiple individuals in the cohort, several shared (i.e., \u201cpublic\u201d) clonotypes were identified with a consistent increase or decrease in frequency across more than one individual; the degree of sharing of these clonotypes was significantly greater than the minimal sharing that would be expected among \u03b3TCR and \u03b4TCR repertoires. An\n in vitro<\/jats:italic>\n analysis of Mtb antigen-reactive \u03b3\u03b4 T cells identified clonotypes that were similar or identical to the single-chain \u03b3TCRs and \u03b4TCRs that changed consistently after BCG vaccination; pairings of \u03b3TCRs and \u03b4TCRs that increased after BCG vaccination were significantly over-represented among the Mtb-reactive \u03b3\u03b4 T cells (p = 1.2e-6).\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n These findings generate hypotheses about specific \u03b3\u03b4TCR clonotypes that may expand in response to BCG vaccination and may recognize Mtb antigens. Future studies are required to validate and characterize these clonotypes, with an aim to better understand the role of \u03b3\u03b4 T cells in Mtb immunity.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1100490","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T01:06:01Z","timestamp":1679965561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of BCG vaccination on the repertoire of human \u03b3\u03b4 T cell receptors"],"prefix":"10.3389","volume":"14","author":[{"given":"Mei","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azra","family":"Blazevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Fiore-Gartland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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