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

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

Author information

1
Department of Medicine, University of Washington Medical Center, 750 Republican Street, Suite E663, Seattle, WA 98115, USA; Department of Pathology, Molecular Medicine and Mechanisms of Disease Program, University of Washington, Seattle, WA 98195, USA.
2
Department of Medicine, University of Washington Medical Center, 750 Republican Street, Suite E663, Seattle, WA 98115, USA.
3
Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
4
Stratingh Institute for Chemistry, University of Groningen, 9747AG Groningen, the Netherlands.
5
School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.
6
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, the Netherlands.
7
Adaptive Biotechnologies, Seattle, WA 98102, USA.
8
South African Tuberculosis Vaccine Initiative and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7935, South Africa.
9
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3010, Australia.
10
Department of Rheumatology, Allergy & Immunology, Brigham and Women's Hospital, 60 Fenwood Road, Room 6006V, Boston, MA 02115, USA.
11
Department of Medicine, University of Washington Medical Center, 750 Republican Street, Suite E663, Seattle, WA 98115, USA. Electronic address: seshadri@uw.edu.
12
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, the Netherlands; Department of Rheumatology, Allergy & Immunology, Brigham and Women's Hospital, 60 Fenwood Road, Room 6006V, Boston, MA 02115, USA. Electronic address: i.vanrhijn@uu.nl.

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 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

PMID:
29398561
PMCID:
PMC5910231
DOI:
10.1016/j.chembiol.2018.01.006
[Indexed for MEDLINE]
Free PMC Article

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