Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin
Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin
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DOI：
10.1073/pnas.040569797
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发表时间：
2000-03-28
影响因子：
11.1
通讯作者：
Vivier, E
中科院分区：
文献类型：
--
作者：
André, P;Spertini, O;Vivier, E
自然杀伤（NK）细胞是先天免疫系统的组成部分，可以识别和杀死病毒感染的细胞，肿瘤细胞和同种异体细胞，而无需事先致敏。NK细胞还产生细胞因子（例如，干扰素-γ和肿瘤坏死因子-α）和趋化因子（例如，巨噬细胞炎性蛋白-1 α），其促进抗原特异性免疫的获得。NK细胞分化伴随着粘蛋白样糖蛋白的细胞表面表达，所述粘蛋白样糖蛋白具有NK细胞限制性硫酸角质素相关的乳糖胺碳水化合物，PENS表位。在这里，我们报告，PENS是一个翻译后修饰的P-选择素糖蛋白配体-1（PSGL-1）。PENS表位在PSGL-1上产生了L-选择素的独特结合位点，其不依赖于PSGL-1酪氨酸硫酸化。在NK细胞表面，PENS的表达与L-选择素的消失和杀伤细胞Ig样受体（KIR）的上调相协调。这些结果表明，NK细胞分化伴随着获得独特的碳水化合物PENS，其可以作为组合代码的一部分将KIR+ NK细胞递送至特定组织。
Natural killer (NK) cells are components of the innate immune system that can recognize and kill virally infected cells, tumor cells, and allogeneic cells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-gamma and tumor necrosis factor-alpha) and chemokines (e.g., macrophage inflammatory protein-1 alpha) that promote the acquisition of antigen-specific immunity. NK cell differentiation is accompanied by the cell surface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PENS epitope. Here, we report that PENS is a post-translational modification of P-selectin glycoprotein ligand-1 (PSGL-1). The PENS epitope creates on PSGL-1 a unique binding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation. On the surface of NK cells, the expression of PENS is coordinated with the disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is accompanied by the acquisition of a unique carbohydrate, PENS, that can serve as part of a combination code to deliver KIR+ NK cells to specific tissues.