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Chancellor, Andrew; Tocheva, Anna S.; Cave-Ayland, Chris; Tezera, Liku; White, Andrew; Dulayymi, Juma’a R. Al; 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 by Mycobacterium tuberculosis mycolic acid meromycolate chains

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  • Medientyp: E-Artikel
  • Titel: CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains
  • Beteiligte: Chancellor, Andrew; Tocheva, Anna S.; Cave-Ayland, Chris; Tezera, Liku; White, Andrew; Dulayymi, Juma’a R. Al; 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: National Academy of Sciences, 2017
  • Erschienen in: Proceedings of the National Academy of Sciences of the United States of America
  • Sprache: Englisch
  • ISSN: 0027-8424; 1091-6490
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <p>Tuberculosis (TB), caused by <italic>Mycobacterium tuberculosis</italic>, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells.</p>
  • Zugangsstatus: Freier Zugang