ArticleThe Journal of experimental medicine2004
Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T cells.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 173 citations in OpenAlex.
- Human CD1c-autoreactive T-cells recogniseeLife · 2026Article
- Polyketide synthase 12 is anbioRxiv : the preprint server for biology · 2026Article
- Gene conversion is a key driver of diversity hotspots inbioRxiv : the preprint server for biology · 2026Article
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.Tuberculosis (Edinburgh, Scotland) · 2025Article
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection inbioRxiv : the preprint server for biology · 2025Article
- CD1-restricted T cells: are unconventional allies the key to future TB vaccines?Frontiers in immunology · 2025Review
- Enhanced analysis of the genomic diversity ofFrontiers in microbiology · 2025Article
- Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells.Clinical immunology (Orlando, Fla.) · 2024Review
- Repurposing a Fully Reducing Polyketide Synthase toward 2-Methyl Guerbet-like Lipids.ACS catalysis · 2024Article
- Antimycobacterial Activities of Hydroxamic Acids and Their Iron(II/III), Nickel(II), Copper(II) and Zinc(II) Complexes.Microorganisms · 2023Article
- Polyketide synthases mutation in tuberculosis transmission revealed by whole genomic sequence, China, 2011-2019.Frontiers in genetics · 2023Article
- Drug-resistant strains ofFrontiers in cellular and infection microbiology · 2023Review
- Discovery of a novel type IIb RelBE toxin-antitoxin system in Mycobacterium tuberculosis defined by co-regulation with an antisense RNA.Molecular microbiology · 2022Article
- Genome-wide estimation of recombination, mutation and positive selection enlightens diversification drivers of Mycobacterium bovis.Scientific reports · 2021Article
- Chemical Synthesis of Cell Wall Constituents ofChemical reviews · 2021Review
- A Unified Approach for the Total Synthesis of cyclo-Archaeol, iso-Caldarchaeol, Caldarchaeol, and Mycoketide.Angewandte Chemie (International ed. in English) · 2021Article
- The role of donor-unrestricted T-cells, innate lymphoid cells, and NK cells in anti-mycobacterial immunity.Immunological reviews · 2021Review
- TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.Nature communications · 2021Article
- Role of Group 1 CD1-Restricted T Cells in Host Defense and Inflammatory Diseases.Critical reviews in immunology · 2021Article
- GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen Mycobacterium leprae.PLoS neglected tropical diseases · 2020Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
CD1c-mediated T cells are activated by a mycobacterial phospholipid antigen whose carbohydrate structure precisely corresponds to mammalian mannosyl beta-1-phosphodolichol (MPD), but contains an unusual lipid moiety. Here, we show that this T cell antigen is a member of a family of branched, alkane lipids that vary in length (C30-34) and are produced by medically important mycobacteria such as M. tuberculosis and M. bovis Bacille-Calmette-Guerin. The alkane moiety distinguished these mycobacterial lipid antigens from mammalian MPDs and was necessary for activation of CD1c-restricted T cells, but could not be accounted for by any known lipid biosynthetic pathway. Metabolic labeling and mass spectrometric analyses suggested a mechanism for elongating lipids using alternating C2 and C3 units, rather than C5 isopentenyl pyrophosphate. Inspection of the M. tuberculosis genome identified one candidate gene, pks12, which was predicted to encode the largest protein in M. tuberculosis, consisting of 12 catalytic domains that correspond to key steps in the proposed pathway. Genetic deletion and complementation showed that Pks12 was necessary for antigen production, but did not affect synthesis of true isoprenols. These studies establish the genetic and enzymatic basis for a previously unknown type of polyketide, designated mycoketide, which contains a lipidic pathogen-associated molecular pattern.
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