Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA 02115.
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2020 Sep 15;117(37):22944-22952. doi: 10.1073/pnas.2010545117. Epub 2020 Aug 31.
γδ T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by Vδ1-expressing γδ T cells is becoming increasingly diverse. Here we describe human γδ T cells that recognize CD1b, a lipid antigen-presenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific γδ T cells use Vδ1. Despite their common use of Vδ1, three CD1b-specific γδ T cell receptors (TCRs) showed clear differences in the surface of CD1b recognized, the requirement for lipid antigens, and corecognition of butryophilin-like proteins. Several Vγ segments were present among the CD1b-specific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the Vδ1 chain. One of the CD1b-specific Vδ1 TCRs paired with Vγ4 and shows dual reactivity to CD1b and butyrophilin-like proteins. αβ TCRs typically recognize the peptide display platform of MHC proteins. In contrast, our results demonstrate the use of rearranged receptors to mediate diverse modes of recognition across the surface of CD1b in ways that do and do not require carried lipids.
γδ T 细胞构成了人类细胞免疫系统的重要组成部分，它们可以对组织损伤、感染和癌症做出反应。目前已知的 Vδ1 表达的 γδ T 细胞识别的分子靶标谱越来越多样化。在这里，我们描述了可以识别 CD1b 的人类 γδ T 细胞，CD1b 是一种可诱导表达于单核细胞和树突状细胞上的脂质抗原呈递分子。我们使用 CD1b 四聚体来研究多个供体，发现许多 CD1b 特异性 γδ T 细胞使用 Vδ1。尽管它们共同使用 Vδ1，但三种 CD1b 特异性 γδ T 细胞受体 (TCR) 在识别 CD1b 的表面、对脂质抗原的需求以及与类似丁酰膦蛋白的共识别方面表现出明显差异。在 CD1b 特异性 TCR 中存在几种 Vγ 片段，但链交换实验表明 CD1b 特异性由 Vδ1 链介导。其中一种 CD1b 特异性 Vδ1 TCR 与 Vγ4 配对，表现出对 CD1b 和类似丁酰膦蛋白的双重反应性。αβ TCR 通常识别 MHC 蛋白的肽展示平台。相比之下，我们的研究结果表明，通过重排的受体可以介导多种识别方式，这些方式可以也可以不依赖于携带的脂质，从而在 CD1b 表面上进行识别。
