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BCG protects nonhuman primates (NHP) against pulmonary and extrapulmonary tuberculosis. In humans and NHP, protection is thought to be mediated by T cells, which typically recognize bacterial peptide Ags bound to MHC proteins. However, during vertebrate evolution, T cells acquired the capacity to recognize lipid Ags bound to CD1a, CD1b, and CD1c proteins expressed on APCs. It is unknown whether BCG induces T cell immunity to mycobacterial lipids and whether CD1-restricted T cells are resident in the lung. In this study, we developed and validated Macaca mulatta (Mamu) CD1b and CD1c tetramers to probe ex vivo phenotypes and functions of T cells specific for glucose monomycolate (GMM), an immunodominant mycobacterial lipid Ag. We discovered that CD1b and CD1c present GMM to T cells in both humans and NHP. We show that GMM-specific T cells are expanded in rhesus macaque blood 4 wk after i.v. BCG, which has been shown to protect NHP with near-sterilizing efficacy upon M. tuberculosis challenge. After vaccination, these T cells are detected at high frequency within bronchoalveolar fluid and express CD69 and CD103, markers associated with resident memory T cells. Thus, our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines, such as BCG, and show that lipid Ag-specific T cells are resident in the lungs, where they may contribute to protective immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.2001065","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T18:39:20Z","timestamp":1612377560000},"page":"1240-1250","source":"Crossref","is-referenced-by-count":25,"title":["T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette\u2013Gu\u00e9rin Vaccination"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-290X","authenticated-orcid":false,"given":"Erik D","family":"Layton","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumik","family":"Barman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-9982","authenticated-orcid":false,"given":"Damien B","family":"Wilburn","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8738-1579","authenticated-orcid":false,"given":"Krystle K Q","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malisa T","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9733-2359","authenticated-orcid":false,"given":"John D","family":"Altman","sequence":"additional","affiliation":[{"name":"National Institutes of Health Tetramer Core Facility, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1359","authenticated-orcid":false,"given":"Thomas J","family":"Scriba","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town 9747 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Tahiri","sequence":"additional","affiliation":[{"name":"Stratingh Institute for Chemistry, University of Groningen 7925 , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-1300","authenticated-orcid":false,"given":"Adriaan J","family":"Minnaard","sequence":"additional","affiliation":[{"name":"Stratingh Institute for Chemistry, University of Groningen 7925 , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Seder","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-2802","authenticated-orcid":false,"given":"Patricia A","family":"Darrah","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-7540","authenticated-orcid":false,"given":"Chetan","family":"Seshadri","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine , Seattle, WA 98109"},{"name":"Tuberculosis Research and Training Center, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"2025030502023595800_r1","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.3389\/fimmu.2017.01134","article-title":"What have we learnt about BCG vaccination in the last 20 years?","volume":"8","author":"Dockrell","year":"2017","journal-title":"Front. 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