2018
DOI: 10.1016/j.chembiol.2018.01.006
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CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis

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 c… Show more

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Cited by 26 publications
(40 citation statements)
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References 57 publications
(91 reference statements)
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“…The development of CD1b tetramers for GMM, SGLs, and MA have enabled the isolation of mycolipid-specific T cells to study the T cell receptor (TCR) repertoire and functional diversity directly ex vivo (35)(36)(37)(38)(39)(40). TCR diversity among T cells specific for mycolipids has been best studied using GMM as the model antigen.…”
Section: Mycolipid-specific T Cell Receptor Diversitymentioning
confidence: 99%
“…The development of CD1b tetramers for GMM, SGLs, and MA have enabled the isolation of mycolipid-specific T cells to study the T cell receptor (TCR) repertoire and functional diversity directly ex vivo (35)(36)(37)(38)(39)(40). TCR diversity among T cells specific for mycolipids has been best studied using GMM as the model antigen.…”
Section: Mycolipid-specific T Cell Receptor Diversitymentioning
confidence: 99%
“…High levels of CD1b are present on DC's or induced on monocytes differentiating into DCs [7,8], where it presents self and foreign lipids to T cells. Many foreign lipids that are known to be presented by CD1b are derived from mycobacteria or closely related actinobacteria, such as glucose monomycolate, glycerol monomycolate [9][10][11], mycolic acid [5,12,13], and diacylated sulfoglycolipids [14,15]. Also, some self-lipids from mammalian cells are presented by CD1b, including phosphatidylglycerol, phosphatidic acid (PA), phosphatidylethanolamine, phosphatidylinositol, and gangliosides [16][17][18][19].…”
Section: Introductionmentioning
confidence: 99%
“…We first determined which co-receptor was expressed by SGL-specific T cells directly ex vivo using CD1b tetramers loaded with a biologically validated synthetic analog of SGL (James et al, 2018). We examined peripheral blood mononuclear cells (PBMC) derived from five U.S. healthy donors, five South African adolescents with latent tuberculosis infection (LTBI), and five South African adolescents without LTBI (Supplemental Table 1, Supplemental Table 2, and Supplemental Figure 1) (Mahomed et al, 2011).…”
Section: Resultsmentioning
confidence: 99%
“…To ensure accurate identification of antigen-specific T cells, we used a dual-tetramer labelling strategy incorporating SGL-CD1b tetramer labeled with two distinct fluorochromes and defined SGL-specific T cells as staining with both tetramers while being unlabeled by a mock-loaded CD1b tetramer (Figure 1A, Supplemental Figure 1). Gates defining SGL-CD1b tetramer-positive cells were set based on staining an SGL-specific T cell line and fluorescence minus one (FMO) controls (Figure 1A) (James et al, 2018). Representative staining from one individual is shown (Figure 1B).…”
Section: Resultsmentioning
confidence: 99%