Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec 1.
αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.
αβ 和 γδ T 细胞是两种不同的 T 细胞谱系，它们可以通过分别使用 αβ 和 γδ T 细胞抗原受体（TCR）来响应不同的抗原（Ags）。在这里，我们描述了一群人类 T 细胞，我们称之为 δ/αβ T 细胞，它们表达的 TCR 由 TCR-δ 可变基因（Vδ1）与连接的 α 和恒定的 α 结构域融合而成，与一系列 TCR-β 链配对。我们证明，这些细胞占所有 Vδ1(+)人类 T 细胞的约 50%，可以识别由人类白细胞抗原（HLA）和 CD1d 分别呈递的肽和脂类抗原。与 I 型自然杀伤 T（NKT）细胞类似，CD1d-脂质 Ag 反应性 δ/αβ T 细胞识别 α-半乳糖基神经酰胺（α-GalCer）；然而，它们对 CD1d 呈递的其他脂质 Ag（如 α-葡糖基神经酰胺）的精细特异性与 I 型 NKT 细胞不同。因此，δ/αβTCR 为人类免疫系统提供了新的抗原特异性模式。此外，我们提供了 δ/αβTCR 与其靶标结合的分子基础，其中 Vδ1 编码区域对 δ/αβTCR 结合有主要贡献。我们的研究结果强调了来自 αβ 和 γδTCR 基因座的成分如何重组以赋予抗原特异性，从而扩展了我们对 T 细胞生物学和 TCR 多样性的理解。
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