Cameron Garth, Pellicci Daniel G, Uldrich Adam P, Besra Gurdyal S, Illarionov Petr, Williams Spencer J, La Gruta Nicole L, Rossjohn Jamie, Godfrey Dale I
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia;
School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
J Immunol. 2015 Nov 15;195(10):4604-14. doi: 10.4049/jimmunol.1501222. Epub 2015 Sep 30.
NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR α-chain usage (Vα14-Jα18 in mice, Vα24-Jα18 in humans). However, these cells have diverse TCR β-chains, including Vβ8, Vβ7, and Vβ2 in mice and Vβ11 in humans, joined to a range of TCR Dβ and Jβ genes. In this study, we demonstrate that TCR β-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids α-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vβ7(+) NKT cells from mice, whereas the α-galactosylceramide analog OCH, with a truncated sphingosine chain, was preferentially recognized by Vβ8(+) NKT cells from mice. We show that the influence of the TCR β-chain is due to a combination of Vβ-, Jβ-, and CDR3β-encoded residues and that these TCRs can recapitulate the selective Ag reactivity in TCR-transduced cell lines. Similar observations were made with human NKT cells where different CDR3β-encoded residues determined Ag preference. These findings indicate that NKT TCR β-chain diversity results in differential and nonhierarchical Ag recognition by these cells, which implies that some Ags can preferentially activate type I NKT cell subsets.
自然杀伤T细胞（NKT细胞）识别由CD1d呈递的基于脂质的抗原。I型NKT细胞因其TCRα链使用情况大多不变（小鼠中为Vα14-Jα18，人类中为Vα24-Jα18），常被称为不变型。然而，这些细胞具有多样的TCRβ链，包括小鼠中的Vβ8、Vβ7和Vβ2以及人类中的Vβ11，它们与一系列TCR Dβ和Jβ基因相连。在本研究中，我们证明TCRβ链组成可以以抗原依赖的方式显著影响脂质抗原的识别。具体而言，糖脂α-葡萄糖神经酰胺和异球三己糖神经酰胺被小鼠的Vβ7(+) NKT细胞优先识别，而具有截短鞘氨醇链的α-半乳糖神经酰胺类似物OCH则被小鼠的Vβ8(+) NKT细胞优先识别。我们表明，TCRβ链的影响是由于Vβ、Jβ和CDR3β编码的残基共同作用，并且这些TCR可以在TCR转导的细胞系中重现选择性抗原反应性。在人类NKT细胞中也有类似的观察结果，其中不同的CDR3β编码残基决定了抗原偏好。这些发现表明，NKT细胞TCRβ链的多样性导致这些细胞对抗原的识别存在差异且无等级之分，这意味着某些抗原可以优先激活I型NKT细胞亚群。
