A common glycan epitope involved in neural cell differentiation and lymphocyte growth

二二酸（diSia）参与神经突分化和T细胞生长，并存在于神经细胞中的一些糖蛋白上，如CD166。CD166是一种细胞粘附分子，常见于哺乳动物脑和T淋巴细胞；然而，diSia对CD166的作用仍不清楚。本研究的目的是了解diSia表位对细胞分化和生长的调控机制。为此，我们做了以下工作：diSia表位刺激神经突形成的分子机制：除了CD166，一个130 kDa的钙粘蛋白被鉴定为含有diSia的糖蛋白。diSia表位存在于钙粘蛋白的o链聚糖上，如CD166。结果表明，至少有两种α2,8-唾液基转移酶参与了diSia的生物合成。此外，在神经突形成初期，diSia表位在神经突出芽部位的脂筏中积累。因此提示CD166上的diSia表位和/或脂筏上的cadherin具有重要的功能。diSia表位介导抗原非依赖性T细胞生长的分子机制：在小鼠T细胞中检测到100 kDa和200 kDa糖蛋白，其中100 kDa糖蛋白为CD166。我们还证明，通过CD3/ cd4连接的抗原非依赖性T细胞增殖与抗disia抗体共孵育大大增强。在此条件下，糖脂和CD166上的diSia表位均增加，同时CD166 mrna表达增加，可能与α2,8-唾液基转移酶有关。此外，糖脂和CD166上的diSia表位在脂筏中富集，表明它们协同作用增强t细胞增殖。

Disialic acid (diSia) is involved in neurite differentiation as well as T cell growth, and present on a few glycoproteins like CD166 in neural cells. CD166 is a cell adhesion molecule commonly occurring in mammalian brain and T lymphocytes ; however, a role of the diSia on CD166 remains unelucidated. The objective of this research project was to understand a regulatory mechanism of cell differentiation and growth by the diSia epitope. For this purpose, we have done the followings :1.Molecular mechanism for stimulation of neurite formation by the diSia epitope :In addition to CD166,a 130 kDa cadherin was identified as a diSia-containing glycoprotein. The diSia epitope is present on O-linked glycan(s) in cadherin, like CD166. The expression of at least two α2,8-sialyltransferases responsible for biosynthesis of the diSia were demonstrated. Moreover, the diSia epitope was accumulated in lipid rafts in budding sites of neurites in the beginning of neurite formation. It is thus suggested that the diSia epitope on CD166 and/or cadherin on the lipid rafts is functionally important.2.Molecular mechanism for an antigen-independent T cell growth by the diSia epitope :In mouse T cells, 100 kDa and 200 kDa glycoproteins were detected, and the 100 kDa-glycoprotein was demonstrated to be CD166. We also demonstrated that an antigen-independent T cell proliferation by the CD3/CD4-ligation was greatly enhanced by co-incubation with anti-diSia antibody. Under the conditions, the diSia epitope on both glycolipids and CD166 was increased, with a concomitant increase in expression of mRNAs for CD166,possibly involved α2,8-sialyltransferases. Furthermore, the diSia epitopes on the glycolipids and CD166 are enriched in lipid rafts, suggesting that they cooperatively operate to enhance the T-cell proliferation.