CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis. Issue 4 (19th April 2018)

• Record Type: Journal Article
• 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
• Is Part Of: Cell chemical biology. Volume 25:Issue 4(2018)
• Page Start: 392
• Page End: 402.e14
• Publication Date: 2018-04-19
• Subjects: human -- T cells -- mycobacteria -- tuberculosis -- antigen-presentation -- CD1 -- T cell receptor -- lipid antigen; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2018.01.006
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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. Graphical Abstract: Highlights: We describe hybrid synthesis of a mycobacterial sulfoglycolipid T cell antigen This sulfoglycolipid (SGL) analog is bioequivalent to the natural compound This antigen was used to generate SGL-loaded CD1b tetramers Tetramers can be used to identify SGL-specific T cells in peripheral blood Abstract : Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis (Mtb) and recognized by human T cells. James, Yu et al. describe a new hybrid synthesis for key antigenic determinants of SGLs and the development of SGL-specific tetramers that can now be applied to large-scale translational studies.