Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells
Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells
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DOI：
10.1093/intimm/dxh299
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Arase, N;Takeuchi, A;Saito, T
NK细胞和CD8(+) T细胞通过细胞间相互作用识别靶细胞后表现出细胞毒性和细胞因子产生。我们使用初始 NK 细胞和活化 NK 细胞之间的 cDNA 扣除来筛选参与这些细胞识别和调节的分子。我们鉴定出 I 类限制性 T 细胞相关分子 (CRTAM)，一种带有两个 Ig 结构域的表面受体，是一种激活后在 NK 细胞和 CD8(+) T 细胞上快速瞬时表达的分子。 CRTAM 在细胞表面以二聚体形式表达，其表达受转录调控。然后，我们使用表达克隆系统进一步鉴定了 Nectin 样 (Necl) 分子 2（一种包含三个 Ig 结构域的受体）作为 CRTAM 的配体。虽然 Necl2 介导同型相互作用，但 CRTAM 与 Necl2 相互作用，但不与 CRTAM 本身相互作用。异型CRTAM-Necl2相互作用比同型Necl2相互作用具有更高的亲和力。尽管NK细胞和CD8+T细胞对表达Necl2的靶细胞的细胞毒功能没有明显改变，但表达CRTAM的T细胞与表达Necl2的细胞紧密结合。 CRTAM(+)细胞不诱导同型聚集，但它们确实与Necl2(+)细胞产生强烈的异型结合，这种结合通过添加CRTAM-Ig融合蛋白而被抑制。这些结果表明CRTAM和Necl2之间的异型相互作用在NK细胞和CD8(+)T细胞受刺激后的粘附、相互作用或迁移中起重要作用。
NK cells and CD8(+) T cells exhibit cytotoxicity and cytokine production upon recognizing target cells through cell-cell interaction. We screened the molecules involved in the recognition and regulation of these cells using cDNA subtraction between naive and activated NK cells. We identified class I-restricted T cell-associated molecule (CRTAM), a two Ig domain-bearing surface receptor, as a molecule rapidly and transiently expressed on NK cells and CD8(+) T cells upon activation. CRTAM is expressed as a dimer on the cell surface, and its expression is transcriptionally regulated. Using an expression-cloning system, we then further identified Nectin-like (Necl) molecule 2, a three Ig domain-containing receptor, as a ligand of CRTAM. While Necl2 mediates homotypic interaction, CRTAM interacts with Necl2 but not with CRTAM itself. The heterotypic CRTAM-Necl2 interaction has a higher affinity than the homotypic Necl2 interaction. Although there was no clear alteration in the cytotoxic function of the NK cells and CD8(+) T cells against the Necl2-expressing target cells, T cells expressing CRTAM tightly bound to Necl2-expressing cells. CRTAM(+) cells did not induce homotypic aggregation but they did exert strong heterotypic binding with Necl2(+) cells, which was inhibited by the addition of the CRTAM-Ig fusion protein. These results suggest that the heterotypic interaction between CRTAM and Necl2 plays an important role in the adhesion, interaction or migration of NK cells and CD8(+) T cells upon stimulation.