CD43-independent augmentation of mouse T-cell function by glycoprotein cleaving enzymes

CD43-independent augmentation of mouse T-cell function by glycoprotein cleaving enzymes
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DOI:
10.1111/j.1365-2567.2006.02419.x
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发表时间:
2006-10-01
期刊:
影响因子:
6.4
通讯作者:
Garcia, Gonzalo G.
Garcia, Gonzalo G.
中科院分区:
医学2区
文献类型:
--
作者:
Berger, Scott B.;Akha, Amir A. Sadighi;Garcia, Gonzalo G.

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先前的研究表明,小鼠CD 4(+)T细胞的功能可以通过一种酶O-唾液酸糖蛋白内肽酶(OSGE)来增强,这种酶可以切割表面CD 43,这表明在老年小鼠T细胞上发现的高水平糖基化CD 43可能有助于免疫衰老。新的结果表明,即使在缺乏CD 43的小鼠中,OSGE也能改善T细胞功能,这表明其他糖蛋白必须有助于OSGE对功能的影响。对其他酶的评估发现,有两种酶在老年T细胞中刺激CD 4活化的能力高于年轻T细胞。其中一种是PNGase F,是一种对N-连接聚糖具有特异性的糖苷酶,另一种是来自鼠伤寒沙门氏菌的ST-Siase(2,3),对α 2,3-连接末端唾液酸残基具有特异性。平行凝集素结合实验表明,老年T细胞中易受PNGase F和ST-Siase(2,3)影响的α 2,3-连接唾液酸残基的去除也高于年轻T细胞。PNGase F和ST-Siase(2,3)改善老年小鼠T细胞功能的优先能力可能涉及切割N-连接或O-连接聚糖或两者上含有α 2,3-连接唾液酸残基的糖蛋白。
Previous work has shown that the function of mouse CD4(+) T cells can be augmented by an enzyme, O-sialoglycoprotein endopeptidase (OSGE), which cleaves surface CD43, suggesting the idea that the high levels of glycosylated CD43 found on T cells from aged mice may contribute to immune senescence. New results now show that OSGE improves T-cell function even in mice lacking CD43, showing that other glycoproteins must contribute to the OSGE effect on function. Evaluation of other enzymes found two whose ability to stimulate CD4 activation was higher in aged than in young T cells. One of these, PNGase F, is a glycosidase specific for N-linked glycans, and the other, ST-Siase(2,3) from Salmonella typhimurium, is specific for alpha 2,3-linked terminal sialic acid residues. Parallel lectin-binding experiments showed that removal of alpha 2,3-linked sialic acid residues vulnerable to PNGase F and ST-Siase(2,3) was also greater in old than in young T cells. The preferential ability of PNGase F and ST-Siase(2,3) to improve the function of T cells from aged mice may involve cleavage of glycoproteins containing alpha 2,3-linked sialic acid residues on N-linked or O-linked glycans or both.