Department of Infectious Diseases and Immunology, Universiteit Utrecht, Yalelaan 1, 3584CL Utrecht, The Netherlands.
Int Immunol. 2013 Feb;25(2):91-8. doi: 10.1093/intimm/dxs092. Epub 2012 Sep 11.
Although CD1d and NKT cells have been proposed to have highly conserved functions in mammals, data on functions of CD1d and NKT cells in species other than humans and rodents are lacking. Upon stimulation with the CD1d-presented synthetic antigen α-galactosylceramide, human and rodent type I invariant NKT cells release large amounts of cytokines. The two bovine CD1D (boCD1D) genes have structural features that suggest that they cannot be translated into functional proteins expressed on the cell surface. Here we provide evidence that despite an intron-exon structure and signal peptide that are different from all other known CD1 genes, boCD1D can be translated into a protein that is expressed on the cell surface. However, in vivo treatment of cattle (Bos taurus) with 0.1, 1, or 10 µg kg⁻¹ of the most commonly used α-galactosylceramide, which has a C26 fatty acid, did not lead to an increase in body temperature and serum cytokine levels of the animals. This lack of reactivity is not due to a complete inability of boCD1d to present glycosphingolipids because α-galactosylceramide variants with shorter fatty acids could be presented by boCD1d to human NKT cells in vitro. This suggests that the natural ligands of boCD1d are smaller lipids.
虽然 CD1d 和 NKT 细胞在哺乳动物中被认为具有高度保守的功能，但在人类和啮齿动物以外的物种中，关于 CD1d 和 NKT 细胞功能的数据尚缺乏。在受到 CD1d 呈递的合成抗原α-半乳糖基神经酰胺的刺激后，人类和啮齿动物 I 型不变 NKT 细胞会释放大量细胞因子。两种牛 CD1D（boCD1D）基因具有结构特征，表明它们不能被翻译成表达在细胞表面的功能性蛋白质。在这里，我们提供的证据表明，尽管 boCD1D 的内含子-外显子结构和信号肽与所有其他已知的 CD1 基因不同，但它可以被翻译成表达在细胞表面的蛋白质。然而，对牛（Bos taurus）进行体内治疗时，使用最常用的α-半乳糖基神经酰胺（具有 C26 脂肪酸），其剂量为 0.1、1 或 10μgkg-1，并不会导致动物体温升高和血清细胞因子水平升高。这种无反应性并不是由于 boCD1d 完全不能呈递糖脂，因为较短脂肪酸的α-半乳糖基神经酰胺变体可以在体外被 boCD1d 呈递给人类 NKT 细胞。这表明 boCD1d 的天然配体是较小的脂质。
