{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:15:16Z","timestamp":1768515316484,"version":"3.49.0"},"posted":{"date-parts":[[2024,8,26]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Novel vaccines targeting the world\u2019s deadliest pathogen\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (\n                  <jats:italic>Mtb<\/jats:italic>\n                  ) are urgently needed as the efficacy of the Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restricted\n                  <jats:italic>Mtb<\/jats:italic>\n                  specific CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells can control intracellular\n                  <jats:italic>Mtb<\/jats:italic>\n                  growth, making HLA-E a promising vaccine target for\n                  <jats:italic>Mtb<\/jats:italic>\n                  . In this study, we evaluated the frequency and phenotype of HLA-E restricted\n                  <jats:italic>Mtb<\/jats:italic>\n                  specific CD4\n                  <jats:sup>+<\/jats:sup>\n                  \/CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. BCG vaccination followed by\n                  <jats:italic>Mtb<\/jats:italic>\n                  challenge in NHPs did not affect the frequency of circulating and local HLA-E\/\n                  <jats:italic>Mtb<\/jats:italic>\n                  CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, and we saw the same in humans receiving BCG. HLA-E\/\n                  <jats:italic>Mtb<\/jats:italic>\n                  T cell frequencies were significantly increased after\n                  <jats:italic>Mtb<\/jats:italic>\n                  challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Together, HLA-E\/\n                  <jats:italic>Mtb<\/jats:italic>\n                  restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after\n                  <jats:italic>Mtb<\/jats:italic>\n                  infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.\n                <\/jats:p>","DOI":"10.1101\/2024.08.26.609630","type":"posted-content","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T09:20:25Z","timestamp":1724923225000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>Mtb<\/i>\n                  specific HLA-E restricted T cells are induced during\n                  <i>Mtb<\/i>\n                  infection but not after BCG administration in non-human primates and humans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0523-8929","authenticated-orcid":false,"given":"Linda","family":"Voogd","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolein","family":"van Wolfswinkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Satti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Dijkman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anele","family":"Gela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista E.","family":"van Meijgaarden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kees L.M.C.","family":"Franken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia L.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom H.M.","family":"Ottenhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1359","authenticated-orcid":false,"given":"Thomas J.","family":"Scriba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"McShane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally A.","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank A.W.","family":"Verreck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone A.","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024082922102011000_2024.08.26.609630v1.1","unstructured":"Global tuberculosis report 2023. Geneva: World Health Organization 2023."},{"key":"2024082922102011000_2024.08.26.609630v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens7010019"},{"key":"2024082922102011000_2024.08.26.609630v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2017.01.030"},{"key":"2024082922102011000_2024.08.26.609630v1.4","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12948"},{"key":"2024082922102011000_2024.08.26.609630v1.5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215496"},{"key":"2024082922102011000_2024.08.26.609630v1.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208268200"},{"key":"2024082922102011000_2024.08.26.609630v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5199"},{"key":"2024082922102011000_2024.08.26.609630v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/35869"},{"key":"2024082922102011000_2024.08.26.609630v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.03.002"},{"key":"2024082922102011000_2024.08.26.609630v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109233"},{"key":"2024082922102011000_2024.08.26.609630v1.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200122"},{"key":"2024082922102011000_2024.08.26.609630v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13591"},{"key":"2024082922102011000_2024.08.26.609630v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747184"},{"key":"2024082922102011000_2024.08.26.609630v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl8881"},{"key":"2024082922102011000_2024.08.26.609630v1.15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5852"},{"key":"2024082922102011000_2024.08.26.609630v1.16","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017650"},{"key":"2024082922102011000_2024.08.26.609630v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004671"},{"key":"2024082922102011000_2024.08.26.609630v1.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000782"},{"key":"2024082922102011000_2024.08.26.609630v1.19","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1382793"},{"key":"2024082922102011000_2024.08.26.609630v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00060"},{"key":"2024082922102011000_2024.08.26.609630v1.21","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg1703"},{"key":"2024082922102011000_2024.08.26.609630v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046120"},{"key":"2024082922102011000_2024.08.26.609630v1.23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006384"},{"key":"2024082922102011000_2024.08.26.609630v1.24","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw2607"},{"key":"2024082922102011000_2024.08.26.609630v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.07.013"},{"key":"2024082922102011000_2024.08.26.609630v1.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe9233"},{"key":"2024082922102011000_2024.08.26.609630v1.27","doi-asserted-by":"publisher","DOI":"10.1177\/135965350501000107"},{"key":"2024082922102011000_2024.08.26.609630v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2712-9_2"},{"key":"2024082922102011000_2024.08.26.609630v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103839"},{"key":"2024082922102011000_2024.08.26.609630v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.04.084"},{"key":"2024082922102011000_2024.08.26.609630v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00143-9"},{"key":"2024082922102011000_2024.08.26.609630v1.32","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12050394"},{"key":"2024082922102011000_2024.08.26.609630v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0319-9"},{"key":"2024082922102011000_2024.08.26.609630v1.34","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9090945"},{"key":"2024082922102011000_2024.08.26.609630v1.35","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24727"},{"key":"2024082922102011000_2024.08.26.609630v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05459-z"},{"key":"2024082922102011000_2024.08.26.609630v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1817-8"},{"key":"2024082922102011000_2024.08.26.609630v1.38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135972"},{"key":"2024082922102011000_2024.08.26.609630v1.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834449100"},{"key":"2024082922102011000_2024.08.26.609630v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535343"},{"key":"2024082922102011000_2024.08.26.609630v1.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9475"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.26.609630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:56:30Z","timestamp":1768460190000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.08.26.609630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,26]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1101\/2024.08.26.609630","relation":{},"subject":[],"published":{"date-parts":[[2024,8,26]]},"subtype":"preprint"}}