Invariant NKT (iNKT) cells in both humans and non-human primates are activated by the glycolipid antigen, α-galactosylceramide (α-GalCer). However, the extent to which the molecular mechanisms of antigen recognition and in vivo phenotypes of iNKT cells are conserved among primate species has not been determined. Using an evolutionary genetic approach, we found a lack of diversifying selection in CD1 genes over 45 million years of evolution, which stands in stark contrast to the history of the MHC system for presenting peptide antigens to T cells. The invariant T cell receptor (TCR)-α chain was strictly conserved across all seven primate clades. Invariant NKT cells from rhesus macaques (Macaca mulatta) bind human CD1D-α-GalCer tetramer and are activated by α-GalCer-loaded human CD1D transfectants. The dominant TCR-β chain cloned from a rhesus-derived iNKT cell line is nearly identical to that found in the human iNKT TCR, and transduction of the rhesus iNKT TCR into human Jurkat cells show that it is sufficient for binding human CD1D-α-GalCer tetramer. Finally, we used a 20-color flow cytometry panel to probe tissue phenotypes of iNKT cells in a cohort of rhesus macaques. We discovered several tissue-resident iNKT populations that have not been previously described in non-human primates but are known in humans, such as TCR-γδ iNKTs. These data reveal a diversity of iNKT cell phenotypes despite convergent evolution of the genes required for lipid antigen presentation and recognition in humans and non-human primates.

中文翻译：

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人类和非人类灵长类动物之间不变 NKT 细胞的分子和细胞表型的保守。


人类和非人类灵长类动物的恒定 NKT (iNKT) 细胞均被糖脂抗原 α-半乳糖神经酰胺 (α-GalCer) 激活。然而，抗原识别的分子机制和 iNKT 细胞的体内表型在灵长类物种中的保守程度尚未确定。使用进化遗传学方法，我们发现 CD1 基因在 4500 万年的进化过程中缺乏多样化的选择，这与 MHC 系统向 T 细胞呈递肽抗原的历史形成鲜明对比。不变的 T 细胞受体 (TCR)-α 链在所有七个灵长类进化枝中都严格保守。来自恒河猴 (Macaca mulatta) 的恒定 NKT 细胞结合人 CD1D-α-GalCer 四聚体，并被装载 α-GalCer 的人 CD1D 转染子激活。从恒河猴衍生的 iNKT 细胞系克隆的显性 TCR-β 链与人 iNKT TCR 中发现的显性 TCR-β 链几乎相同，将恒河猴 iNKT TCR 转导到人 Jurkat 细胞中表明它足以结合人 CD1D-α- GalCer 四聚体。最后，我们使用 20 色流式细胞仪检测一组恒河猴中 iNKT 细胞的组织表型。我们发现了一些组织驻留的 iNKT 群体，这些群体以前在非人类灵长类动物中没有被描述过，但在人类中是已知的，例如 TCR-γδ iNKT。这些数据揭示了 iNKT 细胞表型的多样性，尽管人类和非人类灵长类动物中脂质抗原呈递和识别所需的基因趋同进化。