Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7
Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7
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DOI：
10.1074/jbc.273.12.7118
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发表时间：
1998-03-20
影响因子：
4.8
通讯作者：
Yoshie, O
中科院分区：
文献类型：
--
作者：
Yoshida, R;Nagira, M;Yoshie, O
次级淋巴组织趋化因子 (SLC) 是最近发现的一种 CC 趋化因子，在多种淋巴组织中持续表达，是淋巴细胞的有效且特异性的趋化因子。 SLC 基因和编码另一种淋巴细胞特异性 CC 趋化因子 EBI1 配体趋化因子 (ELC) 的基因在人类染色体 9p13 处形成一个微型簇。在这里，我们证明 SLC 是趋化因子受体 7 (CCR7) 的高亲和力功能配体，在 T 和 B 淋巴细胞上表达，也是 ELC 的已知受体。 SLC 在稳定表达人 CCR7 的鼠 L1.2 细胞中诱导强烈的钙动员。标记有分泌型碱性磷酸酶 (SLC-SEAP) 的 SLC 显示出与 CCR7 的特异性结合，并被 SLC 完全竞争，IC50 为 0.5 nM。 SLC 还在表达 CCR7 的 L1.2 细胞中诱导了强烈的趋化反应，具有典型的钟形剂量反应曲线和 10 nM 的最大迁移。当使用 CCR7 转染的 L1.2 细胞进行评估时，SLC 和 ELC 在通过 CCR7 进行钙动员的交叉脱敏、与 CCR7 结合的交叉竞争以及通过 CCR7 诱导趋化性方面基本相同。 SLC 和 ELC 还被证明完全共享已知表达 CCR7 的培养正常 T 细胞上表达的受体。然而，值得注意的是，当使用培养的正常 T 细胞进行评估时，SLC 在钙动员方面与 ELC 的交叉脱敏以及与 ELC 的交叉竞争结合方面效率较低。因此，SLC 和 ELC 尽管仅具有 32% 的氨基酸同一性，但构成了遗传和功能高度相关的 CC 趋化因子亚组。
Secondary Lymphoid-tissue Chemokine (SLC) is a recently identified CC chemokine that is constitutively expressed in various lymphoid tissues and is a potent and specific chemoattractant for lymphocytes. The SLC gene and the gene encoding another lymphocyte-specific CC chemokine, EBI1-ligand chemokine (ELC), form a mini-cluster at human chromosome 9p13. Here, we show that SLC is a high affinity functional ligand for chemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes and a known receptor for ELC. SLC induced a vigorous calcium mobilization in murine L1.2 cells stably expressing human CCR7. SLC tagged with the secreted form of alkaline phosphatase (SLC-SEAP) showed specific binding to CCR7 that was fully competed by SLC with an IC50 of 0.5 nM. SLC also induced a vigorous chemotactic response in CCR7-expressing L1.2 cells with a typical bell-shaped dose-response curve and a maximal migration at 10 nM. When assessed using CCR7-transfected L1.2 cells, SLC and ELC were essentially equivalent in terms of cross desensitization in calcium mobilization via CCR7, cross-competition in binding to CCR7, and induction of chemotaxis via CCR7. SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7. Notably, however, SLC was somehow less efficient in cross-desensitization against ELC in calcium mobilization and in cross-competition with ELC for binding when assessed using cultured normal T cells. Thus, SLC and ELC, even though sharing only 32% amino acid identity, constitute a genetically and functionally highly related subgroup of CC chemokines.