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Chancellor, Andrew; Tocheva, Anna S.; Cave-Ayland, Chris; Tezera, Liku; White, Andrew; Al Dulayymi, Juma’a R.; Bridgeman, John S.; Tews, Ivo; Wilson, Susan; Lissin, Nikolai M.; Tebruegge, Marc; Marshall, Ben; Sharpe, Sally; Elliott, Tim; Skylaris, Chris-Kriton; Essex, Jonathan W.; Baird, Mark S.; Gadola, Stephan; Elkington, Paul; Mansour, Salah

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

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  • Medientyp: E-Artikel
  • Titel: CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains
  • Beteiligte: Chancellor, Andrew; Tocheva, Anna S.; Cave-Ayland, Chris; Tezera, Liku; White, Andrew; Al Dulayymi, Juma’a R.; Bridgeman, John S.; Tews, Ivo; Wilson, Susan; Lissin, Nikolai M.; Tebruegge, Marc; Marshall, Ben; Sharpe, Sally; Elliott, Tim; Skylaris, Chris-Kriton; Essex, Jonathan W.; Baird, Mark S.; Gadola, Stephan; Elkington, Paul; Mansour, Salah
  • Erschienen: Proceedings of the National Academy of Sciences, 2017
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.1708252114
  • ISSN: 0027-8424; 1091-6490
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Significance</jats:title><jats:p>Tuberculosis is a major global pandemic responsible for more deaths than any other infectious disease, yet no effective vaccine exists. Here, we demonstrate CD1b expression within human tuberculous granulomas, supporting a role for CD1b lipid antigen presentation in host immunity to infection. CD1b presents mycolates, the dominant<jats:italic>Mycobacterium tuberculosis</jats:italic>(Mtb) cell wall lipid class and key virulence factors, to αβ T cells. We reveal that mycolate tail moieties, distal to the head group, are antigenic determinants for the conserved human germline-encoded mycolyl lipid-reactive (GEM) T cell receptors (TCRs). Computational simulations suggest a putative mechanism whereby lipid-ligand dynamics within CD1b regulate GEM-TCR activity. This work provides insights for the development of major histocompatibility complex (MHC)-independent Mtb lipid vaccines, including those that target GEM T cells.</jats:p>
  • Zugangsstatus: Freier Zugang