{"doi":"10.3389/fimmu.2020.556695","title":"Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans","abstract":"MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR -chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-RU tetramer labelling and of the TRAV1-2+ MAIT cells defined by expression of TRAV1-2 and high expression of CD26 and CD161 (TRAV1-2+CD161++CD26++ cells). We analysed postnatal expansion, maturation and functionality of peripheral blood MR1-5-OP-RU tetramer+ MR1T cells in cohorts from three different geographic settings with different tuberculosis (TB) vaccination practices, levels of exposure to and infection with M. tuberculosis. Early after birth, frequencies of MR1-5-OP-RU tetramer+ MR1T cells increased rapidly by several fold. This coincided with the transition from a predominantly CD4+ and TRAV1-2- population in neonates, to a predominantly TRAV1-2+CD161++CD26++ CD8+ population. We also observed that tetramer+ MR1T cells that expressed TNF upon mycobacterial stimulation were very low in neonates, but increased ~10-fold in the first year of life. These functional MR1T cells in all age groups were MR1-5-OP-RU tetramer+TRAV1-2+ and highly expressed CD161 and CD26, markers that appeared to signal phenotypic and functional maturation of this cell subset. This age-associated maturation was also marked by the loss of naïve T cell markers on tetramer+ TRAV1-2+ MR1T cells more rapidly than tetramer+TRAV1-2- MR1T cells and non-MR1T cells. These data suggest that neonates have infrequent populations of MR1T cells with diverse phenotypic attributes; and that exposure to the environment rapidly and preferentially expands the MR1-5-OP-RU tetramer+TRAV1-2+ population of MR1T cells, which becomes the predominant population of functional MR1T cells early during childhood.","journal":"Frontiers in Immunology","year":2020,"id":100979,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":495160,"name":"Anele Gela","orcid":"0000-0003-1473-9204","position":1,"is_corresponding":false},{"id":496403,"name":"Meghan Cansler","orcid":null,"position":2,"is_corresponding":false},{"id":495161,"name":"Megan Null","orcid":"0009-0001-9584-4606","position":3,"is_corresponding":false},{"id":496404,"name":"Rowan B. Duncan","orcid":null,"position":4,"is_corresponding":false},{"id":424014,"name":"Elisa Nemes","orcid":"0000-0003-1662-4961","position":5,"is_corresponding":false},{"id":371678,"name":"Muki Shey","orcid":"0000-0002-8776-4737","position":6,"is_corresponding":false},{"id":253371,"name":"Mary Nsereko","orcid":null,"position":7,"is_corresponding":false},{"id":459416,"name":"Harriet Mayanja‐Kizza","orcid":"0000-0002-9297-6208","position":8,"is_corresponding":false},{"id":495162,"name":"Sarah Kiguli","orcid":"0000-0002-8764-4161","position":9,"is_corresponding":false},{"id":496405,"name":"Jeffrey L. Koh","orcid":null,"position":10,"is_corresponding":false},{"id":250377,"name":"Willem A. Hanekom","orcid":"0000-0003-3070-6154","position":11,"is_corresponding":false},{"id":231909,"name":"Mark Hatherill","orcid":"0000-0003-3491-1809","position":12,"is_corresponding":false},{"id":470888,"name":"Christina Lancioni","orcid":"0000-0002-0821-1211","position":13,"is_corresponding":false},{"id":292892,"name":"David Lewinsohn","orcid":"0000-0001-9906-9494","position":14,"is_corresponding":false},{"id":252307,"name":"Thomas J. Scriba","orcid":"0000-0002-0641-1359","position":15,"is_corresponding":false},{"id":449271,"name":"Deborah A. Lewinsohn","orcid":"0000-0003-1349-3775","position":16,"is_corresponding":false},{"id":495159,"name":"Gwendolyn Swarbrick","orcid":"0000-0001-5786-1256","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T22:39:38.259162Z","pmid":"33042140","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":[]}