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CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis.

TitleCD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsJames, C. A., Yu K. K. Q., Gilleron M., Prandi J., Yedulla V. R., Moleda Z. Z., Diamanti E., Khan M., Aggarwal V. K., Reijneveld J. F., Reinink P., Lenz S., Emerson R. O., Scriba T. J., Souter M. N. T., Godfrey D. I., Pellicci D. G., D Moody B., Minnaard A. J., Seshadri C., & Van Rhijn I.
JournalCell Chem Biol
Volume25
Issue4
Pagination392-402.e14
Date Published2018 Apr 19
ISSN2451-9448
Abstract

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.

DOI10.1016/j.chembiol.2018.01.006
Alternate JournalCell Chem Biol
PubMed ID29398561
PubMed Central IDPMC5910231
Grant ListR01 AI125189 / AI / NIAID NIH HHS / United States
T32 GM095421 / GM / NIGMS NIH HHS / United States

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