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We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to \u201cresist\u201d\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tuberculosis<\/jats:italic>\n                    infection (resisters; RSTRs) and showed that these individuals harbor IFN-\u03b3\u2013independent T cell responses to\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tuberculosis<\/jats:italic>\n                    \u2013specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and \u201cresistance\u201d to\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tuberculosis<\/jats:italic>\n                    infection. Peripheral blood frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor \u03b1\/T cell receptor \u03b4 (TCR\u03b1\/\u03b4) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tuberculosis<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166505","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T14:00:34Z","timestamp":1715090434000},"source":"Crossref","is-referenced-by-count":20,"title":["MR1-restricted T cell clonotypes are associated with \u201cresistance\u201d to Mycobacterium tuberculosis infection"],"prefix":"10.1172","volume":"9","author":[{"given":"Deborah L.","family":"Cross","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik D.","family":"Layton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle K.Q.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malisa T.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa S.","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamin","family":"Li","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise C.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude G.","family":"Chapuis","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Mayanja-Kizza","sequence":"additional","affiliation":[{"name":"Department of Medicine, Makerere University, Kampala, Uganda."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Medicine and"},{"name":"Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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