Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy, Harvard Medical School, Boston, MA, USA.
Eur J Immunol. 2019 May;49(5):737-746. doi: 10.1002/eji.201847949. Epub 2019 Mar 20.
Lyme disease is a common multisystem disease caused by infection with a tick-transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL-II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL-II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b-BbGL-II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL-II-like molecules using tetramers and activation assays revealed a concomitant response to CD1b-expressing APCs in absence of BbGL-II. Further, among all major classes of self-lipid tested, BbGL-II responsive TCRs show strong cross-reactivity to diacylglycerol, a self-lipid antigen with structural similarities to BbGL-II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross-reactive CD1b-restricted T cell responses to bacterial and self-antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross-reactive T cells.
莱姆病是一种常见的多系统疾病，由感染蜱传播的螺旋体伯氏疏螺旋体和相关的伯氏疏螺旋体引起。单糖基二酰基甘油，称为伯氏疏螺旋体糖脂 II（BbGL-II），是感染个体血清中抗体的主要靶标。在这里，我们表明 CD1b 将 BbGL-II 呈递给人类 T 细胞，并且 TCR 介导识别。然而，与对照组相比，我们并未在莱姆病患者的外周血中检测到 BbGL-II 结合 T 细胞的频率增加。出乎意料的是，使用四聚体和激活测定法对 BbGL-II 样分子的 T 细胞特异性进行映射，揭示了在没有 BbGL-II 的情况下，对表达 CD1b 的 APC 的伴随反应。此外，在所测试的所有主要自身脂质类别中，BbGL-II 反应性 TCR 对二酰基甘油表现出强烈的交叉反应性，二酰基甘油是一种自身脂质抗原，与 BbGL-II 具有结构相似性。在 MHC 和 CD1b、CD1c 和 CD1d 蛋白的先前工作的基础上，这项研究提供了证据表明，对细菌和自身抗原存在交叉反应性的 CD1b 限制性 T 细胞反应，并确定了用于未来发现自身和外来抗原交叉反应性 T 细胞的化学定义靶标。
