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哺乳动物物种间CD1细胞内运输模式的保守性。

Conservation of CD1 intracellular trafficking patterns between mammalian species.

作者信息

Dascher Christopher C, Hiromatsu Kenji, Xiong Xiaowei, Sugita Masahiko, Buhlmann Janet E, Dodge Ingrid L, Lee Stella Y, Roura-Mir Carme, Watts Gerald F, Roy Christopher J, Behar Samuel M, Clemens Daniel L, Porcelli Steve A, Brenner Michael B

机构信息

Division of Rheumatology, Immunology and Allergy, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

J Immunol. 2002 Dec 15;169(12):6951-8. doi: 10.4049/jimmunol.169.12.6951.

Abstract

Dendritic cells (DC) are potent APCs that sample Ags from the surrounding environment and present them to naive T cells using cell surface Ag-presenting molecules. The DC in both lymphoid and nonlymphoid tissues express high levels of CD1, a cell surface glycoprotein capable of presenting lipids and glycolipids to T cells. Distinct group 1 CD1 isoforms (CD1a, -b, -c) in man are known to traffic to different parts of the endocytic system where microbial Ags may be sampled. Guinea pigs are the only known rodent species that express the group 1 CD1 proteins. Therefore, we examined the expression and trafficking of guinea pig CD1 (gpCD1) isoforms on isolated DC. Confocal microscopy using mAbs specific for individual gpCD1 isoforms revealed differential trafficking of two distinct CD1b isoforms within DC. Colocalization of MHC class II was observed with the gpCD1b1 isoform, consistent with localization in the late endosomes of DC. In contrast, the gpCD1b3 isoform lacks an endosomal sorting motif and remains on the cell surface. Following incubation with Mycobacterium tuberculosis lipoarabinomannan, colocalization of endocytosed lipoarabinomannan with the gpCD1b1 isoform was observed but not with the gpCD1b3 isoform, which remained primarily on the cell surface. These data demonstrate that guinea pig DC express CD1 isoforms with unique trafficking patterns that recapitulate the patterns seen for human CD1 isoforms. This suggests evolutionary pressure for a conserved mechanism in mammals that allows CD1 to sample lipid Ags from various subcompartments of the endocytic system.

摘要

树突状细胞(DC)是强大的抗原呈递细胞,可从周围环境中摄取抗原,并使用细胞表面抗原呈递分子将其呈递给初始T细胞。淋巴组织和非淋巴组织中的DC均高表达CD1,这是一种能够将脂质和糖脂呈递给T细胞的细胞表面糖蛋白。已知人类中不同的1型CD1亚型(CD1a、-b、-c)会转运至内吞系统的不同部位,在那里可能摄取微生物抗原。豚鼠是已知唯一表达1型CD1蛋白的啮齿动物物种。因此,我们研究了豚鼠CD1(gpCD1)亚型在分离的DC上的表达和转运情况。使用针对单个gpCD1亚型的单克隆抗体进行共聚焦显微镜检查,发现DC内两种不同的CD1b亚型存在差异转运。观察到MHC II类与gpCD1b1亚型共定位,这与在DC晚期内体中的定位一致。相比之下,gpCD1b3亚型缺乏内体分选基序,保留在细胞表面。用结核分枝杆菌脂阿拉伯甘露聚糖孵育后,观察到内吞的脂阿拉伯甘露聚糖与gpCD1b1亚型共定位,但与主要保留在细胞表面的gpCDl3亚型没有共定位。这些数据表明,豚鼠DC表达具有独特转运模式的CD1亚型,重现了人类CD1亚型的模式。这表明哺乳动物中存在一种保守机制的进化压力,使CD1能够从内吞系统的各个亚区室摄取脂质抗原。

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