Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA.
Institute of Immunology, Hannover Medical School, Hannover, D-30625, Germany.
Nat Commun. 2021 Apr 16;12(1):2308. doi: 10.1038/s41467-021-22589-z.
Conventional T cells are selected by peptide-MHC expressed by cortical epithelial cells in the thymus, and not by cortical thymocytes themselves that do not express MHC I or MHC II. Instead, cortical thymocytes express non-peptide presenting MHC molecules like CD1d and MR1, and promote the selection of PLZF iNKT and MAIT cells, respectively. Here, we report an inducible class-I transactivator mouse that enables the expression of peptide presenting MHC I molecules in different cell types. We show that MHC I expression in DP thymocytes leads to expansion of peptide specific PLZF innate-like (PIL) T cells. Akin to iNKT cells, PIL T cells differentiate into three functional effector subsets in the thymus, and are dependent on SAP signaling. We demonstrate that PIL and NKT cells compete for a narrow niche, suggesting that the absence of peptide-MHC on DP thymocytes facilitates selection of non-peptide specific lymphocytes.
传统 T 细胞是由胸腺皮质上皮细胞表达的肽-MHC 选择的，而不是由不表达 MHC I 或 MHC II 的皮质胸腺细胞选择的。相反，皮质胸腺细胞表达非肽呈递 MHC 分子，如 CD1d 和 MR1，并分别促进 PLZF iNKT 和 MAIT 细胞的选择。在这里，我们报告了一种可诱导的 I 类转录激活子小鼠，它可以使不同细胞类型表达肽呈递 MHC I 分子。我们表明，DP 胸腺细胞中 MHC I 的表达导致肽特异性 PLZF 固有样 (PIL) T 细胞的扩增。与 iNKT 细胞类似，PIL T 细胞在胸腺中分化为三个功能效应亚群，并且依赖于 SAP 信号。我们证明 PIL 和 NKT 细胞竞争一个狭窄的小生境，这表明 DP 胸腺细胞上缺乏肽-MHC 有利于非肽特异性淋巴细胞的选择。
