Recognition of lyso-phospholipids by human natural killer T lymphocytes.
Recognition of lyso-phospholipids by human natural killer T lymphocytes.
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DOI：
10.1371/journal.pbio.1000228
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发表时间：
2009-10
期刊：
影响因子：
9.8
通讯作者：
Gumperz JE
中科院分区：
文献类型：
--
作者：
Fox LM;Cox DG;Lockridge JL;Wang X;Chen X;Scharf L;Trott DL;Ndonye RM;Veerapen N;Besra GS;Howell AR;Cook ME;Adams EJ;Hildebrand WH;Gumperz JE
通过鉴定脂质LPC作为内源性抗原，由人NKT细胞的不变子集识别，本研究建立了这些免疫调节细胞和炎症脂质介质之间的新联系。自然杀伤T（NKT）细胞是具有强效免疫调节特性的T淋巴细胞亚群。识别CD 1d分子呈递的自身抗原是NKT细胞活化的重要途径;然而，刺激人NKT细胞的特异性自身抗原的分子身份仍不清楚。在这里，我们分析了人NKT细胞识别CD 1d细胞配体。溶血磷脂酰胆碱（LPC）是最明显的抗原种类。双酰化磷脂酰胆碱和溶血磷酸甘油不同的化学头组刺激只有微弱的反应，从人类NKT细胞。然而，溶血鞘磷脂，共享LPC的磷酸胆碱头基，也激活NKT细胞。抗原呈递细胞与LPC脉冲能够刺激NKT细胞克隆和新鲜分离的外周血淋巴细胞的细胞因子反应增加。这些结果表明，人NKT细胞识别胆碱化溶血磷脂作为由CD 1d呈递的抗原。由于这些溶血磷脂在正常生理过程中充当脂质信使，并且在炎症反应期间以升高的水平存在，因此这些发现指出了NKT细胞和与人类疾病病理生理学相关的细胞信号传导途径之间的新联系。免疫学的一个中心原则是，保护我们免受病原体侵害的细胞反应是由外来化合物（抗原）的分子识别引起的。自身抗原在免疫激活中的作用尚不清楚。我们在这里表明，一种称为溶血磷脂酰胆碱（LPC）的内源性脂质被称为自然杀伤T（NKT）细胞的人T淋巴细胞亚群识别为抗原，特别是被称为不变NKT（iNKT）细胞的这些细胞的最佳研究亚群。NKT细胞引起了免疫学家的兴趣，因为它们可以有效地影响各种免疫反应的结果;例如，它们可以促进细菌清除和肿瘤排斥，它们还可以平息自身免疫性疾病病理。先前的研究表明，NKT细胞被自身抗原激活，但相关化合物的身份仍不清楚。我们发现LPC是iNKT细胞的自身抗原，这表明这些淋巴细胞与高度保守的脂质信号通路相协调，这些脂质信号通路是正常生理过程的基础，并且在炎症期间显著上调。因此，这些结果为理解iNKT细胞如何促进各种免疫反应提供了新的分子基础。
By identifying the lipid LPC as an endogenous antigen, recognized by the invariant subset of human NKT cells, this study establishes a novel link between these immunoregulatory cells and an inflammatory lipid mediator. Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology. A central tenet of immunology is that cellular responses that protect us from pathogens result from molecular recognition of foreign compounds (antigens). The role of self-antigens in immune activation is less clear. We show here that an endogenous lipid called lyso-phosphatidylcholine (LPC) is recognized as an antigen by a subpopulation of human T lymphocytes, called natural killer T (NKT) cells, and specifically by the best-studied subgroup of these cells known as invariant NKT (iNKT) cells. NKT cells have attracted the interest of immunologists because they can potently influence the outcome of diverse immune responses; for example, they can promote bacterial clearance and tumor rejection, and they can also quell autoimmune disease pathology. Previous studies indicated that NKT cells are activated by self-antigens, but the identity of the relevant compounds remained unclear. Our finding that LPC is a self-antigen for iNKT cells suggests that these lymphocytes are attuned to highly conserved lipid signaling pathways that are fundamental to normal physiological processes and are markedly up-regulated during inflammation. Thus, these results provide a new molecular basis for understanding how iNKT cells contribute to a wide variety of immune responses.
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影响因子：
5.5
作者：
Chen, Xiuxu;Wang, Xiaohua;Gumperz, Jenny E.
通讯作者：
Gumperz, Jenny E.
影响因子：
6.5
作者：
Abe, A;Poucher, HK;Shayman, JA
通讯作者：
Shayman, JA
影响因子：
15.3
作者：
Kjer-Nielsen, L;Borg, NA;McCluskey, J
通讯作者：
McCluskey, J
影响因子：
30.5
作者：
Kinjo, Yuki;Tupin, Emmanuel;Kronenberg, Mitchell
通讯作者：
Kronenberg, Mitchell
通过靶向独特的无引起的CD1D反应T细胞群体对硫化物的反应性，预防自身免疫性。
影响因子：
15.3
作者：
Jahng, A;Maricic, I;Aguilera, C;Cardell, S;Halder, RC;Kumar, V
通讯作者：
Kumar, V