Journal
CELL CHEMICAL BIOLOGY
Volume 25, Issue 4, Pages 392-+Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2018.01.006
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Funding
- University of Washington Department of Medicine
- Royalty Research Fund
- U.S. NIH [R01 AI-125189]
- Doris Duke Charitable Foundation
- Bill and Melinda Gates Foundation Vaccine Accelerator Award
- National Health and Medical Research Council of Australia [NHMRC 1113293]
- Australian Research Council (ARC) [CE140100011]
- NHMRC [1117766]
- Molecular Medicine Training grant [T32 GM095421 07]
- Nederlands wetenschappelijk onderzoek (NWO) CW [Toppunt 15.002]
- ALW [824.02.002]
- National Health and Medical Research Council of Australia [1117766] Funding Source: NHMRC
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Mycobacterial cell wall lipids bind the conserved CD1 family of antigen-presenting molecules and activate T cells via their T cell receptors (TCRs). Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis, but tools to study SGL-specific T cells in humans are lacking. We designed a novel hybrid synthesis of a naturally occurring SGL, generated CD1b tetramers loaded with natural or synthetic SGL analogs, and studied the molecular requirements for TCR binding and T cell activation. Two T cell lines derived using natural SGLs are activated by synthetic analogs independently of lipid chain length and hydroxylation, but differentially by saturation status. By contrast, two T cell lines derived using an unsaturated SGL synthetic analog were not activated by the natural antigen. Our data provide a bioequivalence hierarchy of synthetic SGL analogs and SGL-loaded CD1b tetramers. These reagents can now be applied to large-scale translational studies investigating the diagnostic potential of SGL-specific T cell responses or SGL-based vaccines.
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