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

Authors:

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

Details:

Cell Chemical Biology, Volume 25, Issue 4, 2018-04-19

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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.