| Literature DB >> 29158404 |
Andrew Chancellor1,2, Anna S Tocheva1, Chris Cave-Ayland3, Liku Tezera1, Andrew White2, Juma'a R Al Dulayymi4, John S Bridgeman5, Ivo Tews6,7, Susan Wilson1,8, Nikolai M Lissin9, Marc Tebruegge1,7,10,11,12,13, Ben Marshall1,7,10, Sally Sharpe2, Tim Elliott7,14, Chris-Kriton Skylaris3,7, Jonathan W Essex3,7, Mark S Baird4, Stephan Gadola1,7,15, Paul Elkington1,7,10,11, Salah Mansour16,7.
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, 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.Entities:
Keywords: CD1b; GEM T cells; Mycobacterium tuberculosis; molecular dynamics; mycolate lipids
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Year: 2017 PMID： 29158404 PMCID： PMC5754766 DOI： 10.1073/pnas.1708252114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205