{"doi":"10.1101/2022.10.12.511825","title":"MR1-restricted T cell clonotypes are associated with ‘resistance’ to <i>M.tuberculosis</i> infection","abstract":"ABSTRACT T cells are required for a protective immune response against the human adapted pathogen Mycobacterium tuberculosis (M.tb). We recently described a cohort of Ugandan household contacts of tuberculosis cases that appear to ‘resist’ M.tb infection (RSTRs) and showed that these individuals harbor IFN-γ independent T cell responses to M.tb-specific peptide antigens. However, T cells also recognize non-protein antigens via antigen presenting systems that are independent of genetic background, leading to their designation as donor-unrestricted T (DURT) cells. We used combinatorial tetramer staining and multi-parameter flow cytometry to comprehensively characterize the association between DURTs and ‘resistance’ to M.tb infection. We did not observe a difference in peripheral blood frequencies of invariant natural killer T (iNKT) cells, germline encoded mycolyl-reactive (GEM) T cells, or γδ T cells between RSTRs and matched controls with latent M.tb infection (LTBIs). However, we did observe a 1.65-fold increase in frequency of circulating MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBI (p=0.03). Multi-modal single cell RNA-sequencing of 18,251 MR1T cells sorted from a subset of donors revealed 5150 clonotypes that expressed a common transcriptional program, the majority of which were private. Deep sequencing of the TCR-α repertoire revealed several DURT clonotypes that were expanded among RSTRs, including at least two MR1T clonotypes. Taken together, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between MR1 clonotypes and ‘resistance’ to M.tb infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300516,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571546,"name":"Erik D. Layton","orcid":"0000-0001-6409-290X","position":1,"is_corresponding":false},{"id":663367,"name":"Krystle K. Q. Yu","orcid":"0000-0001-8738-1579","position":2,"is_corresponding":false},{"id":664158,"name":"Malisa T. Smith","orcid":null,"position":3,"is_corresponding":false},{"id":571545,"name":"Melissa S. Aguilar","orcid":"0000-0002-1064-899X","position":4,"is_corresponding":false},{"id":298391,"name":"Shamin Li","orcid":"0000-0001-7669-7391","position":5,"is_corresponding":false},{"id":459416,"name":"Harriet Mayanja‐Kizza","orcid":"0000-0002-9297-6208","position":6,"is_corresponding":false},{"id":231947,"name":"Catherine M. Stein","orcid":"0000-0002-9763-5023","position":7,"is_corresponding":false},{"id":231891,"name":"W. Henry Boom","orcid":"0000-0001-5760-9595","position":8,"is_corresponding":false},{"id":445178,"name":"Thomas R. Hawn","orcid":"0000-0003-2368-3185","position":9,"is_corresponding":false},{"id":114739,"name":"Philip Bradley","orcid":"0000-0002-0224-6464","position":10,"is_corresponding":false},{"id":272540,"name":"Evan W. Newell","orcid":"0000-0002-2889-243X","position":11,"is_corresponding":false},{"id":377302,"name":"Chetan Seshadri","orcid":"0000-0003-2783-7540","position":12,"is_corresponding":false},{"id":423074,"name":"Deborah L Cross","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}