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

作者：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^*

来源：Cell Chemical Biology, 2018, 25(4): 392-+.

DOI：10.1016/j.chembiol.2018.01.006

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.

• 出版日期2018-4-19