{"doi":"10.1172/jci185443","title":"A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant trehalose monomycolate","abstract":"Mycobacterium tuberculosis causes human tuberculosis (TB). As mycobacteria are protected by a thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors. Although a few mycobacterial lipid antigens activate unconventional T cells, the antigenicity of most adjuvantic lipids is unknown. Here, we identified that trehalose monomycolate (TMM), an abundant mycobacterial adjuvant, activated human T cells bearing a unique αβ T cell receptor (αβTCR). This recognition was restricted by CD1b, a monomorphic antigen-presenting molecule conserved in primates but not mice. Single-cell TCR-RNA-Seq using newly established CD1b-TMM tetramers revealed that TMM-specific T cells were present as CD4+ effector memory T cells in the periphery of uninfected donors but expressed IFN-γ, TNF, and anti-mycobacterial effectors upon TMM stimulation. TMM-specific T cells were detected in cord blood and PBMCs of donors without bacillus Calmette-Guérin vaccination but were expanded in patients with active TB. A cryo-electron microscopy study of CD1b-TMM-TCR complexes revealed unique antigen recognition by conserved features of TCRs, positively charged CDR3α, and long CDR3β regions. These results indicate that humans have a commonly shared and preformed CD4+ T cell subset recognizing a typical mycobacterial adjuvant as an antigen. Furthermore, the dual role of TMM justifies reconsideration of the mechanism of action of adjuvants.","journal":"Journal of Clinical Investigation","year":2024,"id":446205,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1263534,"name":"Minori Asa","orcid":null,"position":1,"is_corresponding":false},{"id":1263035,"name":"Mika Hirose","orcid":"0000-0001-8991-587X","position":2,"is_corresponding":false},{"id":1263535,"name":"Wakana Kusuhara","orcid":null,"position":3,"is_corresponding":false},{"id":946478,"name":"Nagatoshi Fujiwara","orcid":"0000-0001-5566-681X","position":4,"is_corresponding":false},{"id":1263536,"name":"Hiroto Tamashima","orcid":null,"position":5,"is_corresponding":false},{"id":1263537,"name":"Takahiro Ikazaki","orcid":null,"position":6,"is_corresponding":false},{"id":1263538,"name":"Shiori Oka","orcid":null,"position":7,"is_corresponding":false},{"id":1263539,"name":"Kota Kuraba","orcid":null,"position":8,"is_corresponding":false},{"id":1263036,"name":"Kentaro Tanaka","orcid":"0000-0001-8645-6436","position":9,"is_corresponding":false},{"id":231958,"name":"Takashi Yoshiyama","orcid":"0000-0002-7278-8816","position":10,"is_corresponding":false},{"id":932079,"name":"Masamichi Nagae","orcid":"0000-0002-5470-3807","position":11,"is_corresponding":false},{"id":1263037,"name":"Yoshihiko Hoshino","orcid":"0000-0002-3132-0715","position":12,"is_corresponding":false},{"id":827150,"name":"Daisuke Motooka","orcid":"0000-0002-4616-9608","position":13,"is_corresponding":false},{"id":252300,"name":"Ildiko Van Rhijn","orcid":"0000-0002-1446-5701","position":14,"is_corresponding":false},{"id":1263038,"name":"Xiuyuan Lu","orcid":"0000-0002-0784-2871","position":15,"is_corresponding":false},{"id":459020,"name":"Eri Ishikawa","orcid":"0000-0002-4922-6751","position":16,"is_corresponding":false},{"id":312635,"name":"D. Branch Moody","orcid":"0000-0003-2306-3058","position":17,"is_corresponding":false},{"id":1263039,"name":"Takayuki Kato","orcid":"0000-0002-7210-9457","position":18,"is_corresponding":false},{"id":1105770,"name":"Shinsuke Inuki","orcid":"0000-0002-7525-1280","position":19,"is_corresponding":false},{"id":1263040,"name":"Go Hirai","orcid":"0000-0003-3420-555X","position":20,"is_corresponding":false},{"id":459021,"name":"Sho Yamasaki","orcid":"0000-0002-5184-6917","position":21,"is_corresponding":false},{"id":158920,"name":"Yuki Sakai","orcid":"0000-0002-8427-4740","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:01:50.465308Z","pmid":"39718834","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":[]}