CD28 T cell costimulatory receptor function is negatively regulated by N-linked carbohydrates
CD28 T cell costimulatory receptor function is negatively regulated by N-linked carbohydrates
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DOI：
10.1016/j.bbrc.2004.03.012
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发表时间：
2004-04-23
影响因子：
3.1
通讯作者：
Ochi, A
中科院分区：
文献类型：
--
作者：
Ma, BY;Mikolajczak, SA;Ochi, A
CD 28是T细胞上表达的细胞表面糖蛋白，其通过其抑制共刺激信号的能力来调节免疫应答。尽管CD 28分子量的近50%是N-聚糖，但CD 28糖基化的生理意义目前尚不清楚。在这份报告中，我们研究了低糖基化野生型CD 28及其剪接变体CD 28 i的功能。当通过CD 28中N-糖基化位点的点突变阻止N-糖基化或通过糖苷酶抑制剂减少N-糖基化时，CD 28与CD 80的结合显著增加。低糖基化CD 28的刺激诱导的IL-2启动子活性大于通过野生型CD 28的刺激诱导的活性。与低糖基化的野生型CD 28不同，CD 28 i的低糖基化不改变CD 28 i的功能。我们的数据表明，CD 28的N-聚糖负调节CD 28/CD 80相互作用，导致CD 28信号转导减弱。还表明N-聚糖在与CD 80/CD 86连接后调节CD 28簇集的密度。结果支持了N-糖基化负调控CD 28介导的T细胞粘附和共刺激的假设。(C)2004年爱思唯尔公司All rights reserved.
CD28 is a cell surface glycoprotein expressed on T cells that modulates immune responses through its ability to transduce costimulatory signals. Even though nearly 50% of the molecular mass of CD28 is N-glycan, the physiological significance of CD28 glycosylation is at present unknown. In this report, we have investigated the function of hypoglycosylated wildtype CD28 and its splice variant, CD28i. When N-glycosylation was prevented through point mutations in N-glycosylation sites in CD28, or reduced by glycosidase inhibitors, the binding of CD28 to CD80 significantly increased. Stimulation of hypoglycosylated CD28 induced IL-2 promoter activity greater than that induced through the stimulation of wildtype CD28. Unlike hypoglycosylated wildtype CD28, hypoglycosylation of CD28i did not alter CD28i functions. Our data indicate that N-glycans of CD28 negatively regulate CD28/CD80 interactions, resulting in diminished CD28 signaling. It is also suggested that N-glycans regulate the density of CD28 clustering upon ligation with CD80/CD86. The results support the hypothesis that the N-glycosylation negatively regulates CD28-mediated T cell adhesion and costimulation. (C) 2004 Elsevier Inc. All rights reserved.