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

Charlotte A James, Krystle K Q Yu, Martine Gilleron, Jacques Prandi, Vijayendar R Yedulla, Zuzanna Z Moleda, Eleonora Diamanti, Momin Khan, Varinder K Aggarwal, Josephine F Reijneveld, Peter Reinink, Stefanie Lenz, Ryan O Emerson, Thomas J Scriba, Michael N T Souter, Dale I Godfrey, Daniel G. Pellicci, D Branch Moody, Adriaan J. Minnaard, Chetan SeshadriIldiko Van Rhijn

    Research output: Contribution to journalArticleAcademicpeer-review

    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.

    Original languageEnglish
    JournalCell Chemical Biology
    Early online date29 Jan 2018
    DOIs
    Publication statusPublished - Apr 2018

    Keywords

    • Journal Article

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