Developmentally regulated glycosylation of the CD8αβ coreceptor stalk modulates ligand binding
Developmentally regulated glycosylation of the CD8αβ coreceptor stalk modulates ligand binding
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DOI：
10.1016/s0092-8674(01)00577-3
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发表时间：
2001-11-16
期刊：
影响因子：
64.5
通讯作者：
Reinherz, EL
中科院分区：
文献类型：
--
作者：
Moody, AM;Chui, D;Reinherz, EL
与细胞分化相关的聚糖结构变化的功能后果是不明确的。在这里，我们研究的作用，聚糖加合物的O-糖基化的多肽柄拴系的CD 8 α β辅助受体的胸腺细胞表面。我们发现，未成熟的CD 4（+）CD 8（+）双阳性胸腺细胞比成熟的CD 8单阳性胸腺细胞更容易结合MHCI四聚体，这种差异结合是由ST 3Gal-1唾液酸转移酶控制的发育程序性O-聚糖修饰决定的。ST 3Gal-1诱导和伴随的核心1唾液酸添加至成熟胸腺细胞上的CD 8 β通过改变CD 8 α β结构域-结构域缔合和/或取向来降低CD 8 α β-MHCI亲合力。因此，CD 8 β茎上的聚糖似乎调节二聚体CD 8球状头部结构域的远端结合表面夹持MHCI的能力。
The functional consequences of glycan structural changes associated with cellular differentiation are ill defined. Herein, we investigate the role of glycan adducts to the O-glycosylated polypeptide stalk tethering the CD8 alpha beta coreceptor to the thymocyte surface. We show that immature CD4(+)CD8(+) double-positive thymocytes bind MHCI tetramers more avidly than mature CD8 single-positive thymocytes, and that this differential binding is governed by developmentally programmed O-glycan modification controlled by the ST3Gal-1 sialyltransferase. ST3Gal-1 induction and attendant core 1 sialic acid addition to CD8 beta on mature thymocytes decreases CD8 alpha beta -MHCI avidity by altering CD8 alpha beta domain-domain association and/or orientation. Hence, glycans on the CD8 beta stalk appear to modulate the ability of the distal binding surface of the dimeric, CD8 globular head domains to clamp MHCI.