CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis,Cell Chemical Biology

当前位置： X-MOL 学术 › Cell Chem. Bio. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2018-02-01 , DOI: 10.1016/j.chembiol.2018.01.006
Charlotte A James ₁ , Krystle K Q Yu ₂ , Martine Gilleron ₃ , Jacques Prandi ₃ , Vijayendar R Yedulla ₄ , Zuzanna Z Moleda ₄ , Eleonora Diamanti ₅ , Momin Khan ₅ , Varinder K Aggarwal ₅ , Josephine F Reijneveld ₆ , Peter Reinink ₆ , Stefanie Lenz ₆ , Ryan O Emerson ₇ , Thomas J Scriba ₈ , Michael N T Souter ₉ , Dale I Godfrey ₉ , Daniel G Pellicci ₉ , D Branch Moody ₁₀ , Adriaan J Minnaard ₄ , Chetan Seshadri ₂ , Ildiko Van Rhijn ₁₁

Affiliation

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.
Department of Medicine, University of Washington Medical Center, 750 Republican Street, Suite E663, Seattle, WA 98115, USA.
Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Stratingh Institute for Chemistry, University of Groningen, 9747AG Groningen, the Netherlands.
School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, the Netherlands.
Adaptive Biotechnologies, Seattle, WA 98102, USA.
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.
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.
Department of Rheumatology, Allergy & Immunology, Brigham and Women's Hospital, 60 Fenwood Road, Room 6006V, Boston, MA 02115, USA.
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.

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 byMycobacterium 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.

中文翻译：

CD1b 四聚体识别 T 细胞，识别来自结核分枝杆菌的天然和合成二酰化磺基糖脂

分枝杆菌细胞壁脂质结合保守的 CD1 抗原呈递分子家族，并通过其 T 细胞受体 (TCR) 激活 T 细胞。磺基糖脂 (SGLs) 是由结核分枝杆菌独特合成的，但缺乏研究人类 SGL 特异性 T 细胞的工具。我们设计了一种天然存在的 SGL 的新型混合合成，生成了装载天然或合成 SGL 类似物的 CD1b 四聚体，并研究了 TCR 结合和 T 细胞活化的分子要求。使用天然 SGL 衍生的两种 T 细胞系被合成类似物激活，与脂质链长度和羟基化无关，但因饱和状态而不同。相比之下，使用不饱和 SGL 合成类似物衍生的两种 T 细胞系没有被天然抗原激活。我们的数据提供了合成 SGL 类似物和负载 SGL 的 CD1b 四聚体的生物等效性等级。这些试剂现在可应用于大规模转化研究，调查 SGL 特异性 T 细胞反应或基于 SGL 的疫苗的诊断潜力。

更新日期：2018-04-19

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11