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

Cell Chem Biol. 2018 Apr 19;25(4):392-402.e14. doi: 10.1016/j.chembiol.2018.01.006. Epub 2018 Feb 1.


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.

Keywords: CD1; T cell receptor; T cells; antigen-presentation; human; lipid antigen; mycobacteria; tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Antigens, Bacterial / immunology*
  • Antigens, CD1 / chemistry
  • Antigens, CD1 / immunology*
  • Cell Line
  • Glycolipids / chemistry
  • Glycolipids / immunology*
  • Humans
  • Lymphocyte Activation*
  • Models, Molecular
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / immunology*
  • Protein Multimerization
  • T-Lymphocytes / immunology*
  • Tuberculosis / immunology*


  • Antigens, Bacterial
  • Antigens, CD1
  • CD1b antigen
  • Glycolipids
  • sulfoglycolipids