Selective Ability of Mouse CD1 to Present Glycolipids: α-Galactosylceramide Specifically Stimulates Vα14+ NK T Lymphocytes
Selective Ability of Mouse CD1 to Present Glycolipids: α-Galactosylceramide Specifically Stimulates Vα14+ NK T Lymphocytes
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DOI：
10.4049/jimmunol.161.7.3271
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发表时间：
1998-10
期刊：
影响因子：
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通讯作者：
N. Burdin;L. Brossay;Y. Koezuka;S. Smiley;M. Grusby;M. Gui;M. Taniguchi;K. Hayakawa;M. Kronenberg
中科院分区：
文献类型：
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作者：
N. Burdin;L. Brossay;Y. Koezuka;S. Smiley;M. Grusby;M. Gui;M. Taniguchi;K. Hayakawa;M. Kronenberg
已知小鼠CD 1（mCD 1）糖蛋白呈递肽，而人CD 1分子呈递糖脂。在小鼠中，mCD 1自身反应性NK T细胞通过分泌大量细胞因子在各种免疫应答中发挥关键作用。本研究旨在确定糖脂是否参与NK T细胞对mCD 1的自动识别。α-半乳糖神经酰胺（α-GalCer）是唯一一种能够通过脾T细胞引发mCD 1限制性应答的糖脂。此外，来自mCD 1缺陷型小鼠的脾T细胞未被α-GalCer刺激，表明应答性T细胞被mCD 1选择。使用cytoflow技术，我们证实，在对α-GalCer的应答中，IFN-γ分泌细胞显示NK T细胞表型。然而，IFN-γ相对于IL-4的优势是由mCD 1 + APC的类型决定的，这表明APC调节NK T细胞产生细胞因子的潜力。在一组10个mCD 1自身反应性T细胞杂交瘤中，只有表达NK T细胞典型Vα 14 J α281 TCR重排的细胞对α-GalCer有反应。用内体酸化抑制剂固定或处理mCD 1 + APC以及使用不能通过内体运输的mCD 1突变体仍允许α-GalCer刺激NK T细胞。因此，糖脂识别不需要内体运输和Ag加工。总之，α-GalCer可能是参与mCD 1介导的NK T细胞刺激的自体配体或糖脂配体的模拟物。
Mouse CD1 (mCD1) glycoproteins are known to present peptides, while human CD1 molecules present glycolipids. In mice, mCD1-autoreactive NK T cells play critical roles in various immune responses, through the secretion of high amounts of cytokines. This study was initiated to determine whether glycolipids are involved in the autorecognition of mCD1 by NK T cells. α-Galactosylceramide (α-GalCer) was the only glycolipid tested capable of eliciting an mCD1-restricted response by splenic T cells. Moreover, splenic T cells derived from mCD1-deficient mice were not stimulated by α-GalCer, suggesting that the responsive T cells are selected by mCD1. Using cytoflow techniques, we confirmed that, in response to α-GalCer, IFN-γ-secreting cells displayed an NK T cell phenotype. The predominance of IFN-γ vs IL-4, however, is determined by the type of mCD1+ APC, suggesting the potential for APC regulation of cytokine production by NK T cells. Among a panel of 10 mCD1-autoreactive T cell hybridomas, only the ones that express the typical Vα14Jα281 TCR rearrangement of NK T cells responded to α-GalCer. Fixation or treatment of mCD1+ APCs with an inhibitor of endosomal acidification and the use of mCD1 mutants unable to traffic through endosome still allowed α-GalCer to stimulate NK T cells. Thus, endosomal trafficking and Ag processing are not required for glycolipid recognition. In summary, α-GalCer might be the autologous ligand, or a mimic of a glycolipid ligand, involved in the mCD1-mediated stimulation of NK T cells.