The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells
The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells
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DOI：
10.1074/jbc.274.37.26259
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发表时间：
1999-09-10
影响因子：
4.8
通讯作者：
Mayer, L
中科院分区：
文献类型：
--
作者：
Campbell, NA;Kim, HS;Mayer, L
先前的研究表明，正常肠上皮细胞（IEC）能够选择性地激活具有抑制活性的CD8（+）T细胞，诱导与CD8相关激酶p56（lck）和T细胞受体（TCR）相关激酶p59（fyn）激活相关的增殖。这个过程似乎部分与 180 kDa IEC 表面糖蛋白 gp180 有关，它与 CDS 结合并激活 CDS 相关的 p56(lck)。然而，单独纯化的 gp180 不能诱导 T 细胞增殖，也不能激活 p59(fyn)。由于 IEC 表达 Ib 类分子 CD1d，并且针对 CD1d 的单克隆抗体 (mAb) 抑制 IEC 诱导的 CD8(+) T 细胞增殖，因此进行了免疫共沉淀和酶联免疫吸附测定研究，结果证明了 IEC 表面上 gp180 和 CD1d 的关联。有趣的是，IEC-T 细胞共培养物中 p59(fyn) 的激活被抗 CD1d mAb D5 阻断，但不被抗 gp180 mAb B9 阻断。相反，用 mAb B9 处理 IEC 可抑制 IEC 诱导的 p56(lck) 激活，但不能抑制 p59(fyn)。更直接地，人 CD1d cDNA (FO-1 D5) 转染子能够激活 p59(fyn)，但不能激活 p56(lck)。这些数据表明IEC表面的CD1d-gp180复合物可以被TCR-CDS共受体识别，从而导致CD8(+) T细胞的激活。
Previous studies have shown that normal intestinal epithelial cells (IECs) are able to selectively activate CD8(+) T cells with suppressor activity, inducing proliferation associated with the activation of both the CD8-associated kinase p56(lck) and the T cell receptor (TCR)associated kinase p59(fyn). This process appears to relate in part to a 180-kDa IEC surface glycoprotein, gp180, which binds to CDS and activates CDS-associated p56(lck). However, purified gp180 alone is unable to induce T cell proliferation and does not activate p59(fyn). Because the class Ib molecule CD1d is expressed by IECs and monoclonal antibodies (mAbs) against CD1d inhibit IEC-induced proliferation of CD8(+) T cells, co-immunoprecipitation and enzyme-linked immunosorbent assay studies were performed, which demonstrated an association of gp180 and CD1d on the IEC surface. Interestingly, the activation of p59(fyn) in IEC-T cell co-cultures was blocked by the anti-CD1d mAb D5 but not by the anti-gp180 mAb B9. Conversely, treatment of IECs with mAb B9 inhibited IEC-induced activation of p56(lck) but not p59(fyn). More directly, a human CD1d cDNA (FO-1 D5) transfectant was able to activate p59(fyn) but not p56(lck). These data suggest that the CD1d-gp180 complex on the surface of IECs can be recognized by the TCR-CDS co-receptor, resulting in the activation of CD8(+) T cells.