Science Immunology ( IF 24.8 ) Pub Date : 2021-06-25 , DOI: 10.1126/sciimmunol.abg4176 Nicholas A Gherardin 1, 2 , Samuel J Redmond 1, 2 , Hamish E G McWilliam 1, 3 , Catarina F Almeida 1, 2 , Katherine H A Gourley 1, 2 , Rebecca Seneviratna 1, 2 , Shihan Li 1, 2 , Robert De Rose 1, 2 , Fiona J Ross 1, 2 , Catriona V Nguyen-Robertson 1, 2 , Shian Su 4, 5 , Matthew E Ritchie 4, 5 , Jose A Villadangos 1, 3 , D Branch Moody 6 , Daniel G Pellicci 1, 2, 7 , Adam P Uldrich 1, 2 , Dale I Godfrey 1, 2
CD1c presents lipid-based antigens to CD1c-restricted T cells, which are thought to be a major component of the human T cell pool. However, the study of CD1c-restricted T cells is hampered by the presence of an abundantly expressed, non–T cell receptor (TCR) ligand for CD1c on blood cells, confounding analysis of TCR-mediated CD1c tetramer staining. Here, we identified the CD36 family (CD36, SR-B1, and LIMP-2) as ligands for CD1c, CD1b, and CD1d proteins and showed that CD36 is the receptor responsible for non–TCR-mediated CD1c tetramer staining of blood cells. Moreover, CD36 blockade clarified tetramer-based identification of CD1c-restricted T cells and improved identification of CD1b- and CD1d-restricted T cells. We used this technique to characterize CD1c-restricted T cells ex vivo and showed diverse phenotypic features, TCR repertoire, and antigen-specific subsets. Accordingly, this work will enable further studies into the biology of CD1 and human CD1-restricted T cells.
中文翻译:
CD36 家族成员是 CD1 抗原呈递分子的 TCR 非依赖性配体
CD1c 将基于脂质的抗原呈递给 CD1c 限制性 T 细胞,这些 T 细胞被认为是人类 T 细胞库的主要成分。然而,CD1c 限制性 T 细胞的研究受到血细胞上 CD1c 大量表达的非 T 细胞受体 (TCR) 配体的存在的阻碍,从而混淆了 TCR 介导的 CD1c 四聚体染色分析。在这里,我们将 CD36 家族(CD36、SR-B1 和 LIMP-2)鉴定为 CD1c、CD1b 和 CD1d 蛋白的配体,并表明 CD36 是负责非 TCR 介导的血细胞 CD1c 四聚体染色的受体。此外,CD36 阻断澄清了基于四聚体的 CD1c 限制性 T 细胞的鉴定,并改进了 CD1b 和 CD1d 限制性 T 细胞的鉴定。我们使用这种技术来表征离体 CD1c 限制性 T 细胞,并显示出不同的表型特征、TCR 库、和抗原特异性亚群。因此,这项工作将使进一步研究 CD1 和人类 CD1 限制性 T 细胞的生物学成为可能。