Potential pathways for regulation of NK and T cell responses:: differential X-linked lymphoproliferative syndrome gene product SAP interactions with SLAM and 2B4
Potential pathways for regulation of NK and T cell responses:: differential X-linked lymphoproliferative syndrome gene product SAP interactions with SLAM and 2B4
复制标题
DOI：
10.1093/intimm/12.12.1749
复制
发表时间：
2000-12-01
影响因子：
4.4
通讯作者：
Terhorst, C
中科院分区：
文献类型：
--
作者：
Say贸s, J;Nguyen, KB;Terhorst, C
SAP是X连锁淋巴增生综合征（XLP）中改变或缺失的基因，其编码包含单个SH 2结构域的小蛋白，并与存在于活化或记忆T和B细胞上的细胞表面蛋白SLAM结合。由于在XLP患者中也报道了NK细胞活性缺陷，我们研究了NK细胞中的SAP基因。在病毒感染SCID小鼠后诱导SAP，并且通过在IL-2存在下体外培养显示SAP在NK细胞中表达。此外，SAP在NK细胞系YT和RNK 16中表达。因为与SAP相互作用的细胞表面蛋白SLAM和与SLAM具有序列同源性的膜蛋白2B 4，也被发现在活化的NK和T细胞群体的表面上表达，它们可能在这些群体中获得SAP功能。然而，我们发现2B 4也结合SAP，2B 4-SAP相互作用仅在2B 4的酪氨酸磷酸化后发生。相反，SLAM-SAP相互作用不依赖于SLAM上Y281和Y327的磷酸化。由于2B 4的配体CD 48在EB病毒（EBV）感染的B细胞的表面上表达，因此SAP可能通过这对细胞表面分子调节信号转导。这些数据支持XLP是缺陷的NK和T淋巴细胞对EBV的应答的结果的假设。改变的应答可能是由于由SLAM-SLAM和2B 4-CD 48相互作用引发的信号级联的异常控制。
SAP, the gene that is altered or absent in the X-linked lymphoproliferative syndrome (XLP), encodes a small protein that comprises a single SH2 domain and binds to the cell-surface protein SLAM which is present on activated or memory T and B cells. Because defective NK cell activity also has been reported in XLP patients, we studied the SAP gene in NK cells. SAP was induced upon viral infection of SCID mice and shown to be expressed in NK cells by in vitro culturing in the presence of IL-2, Moreover, SAP was expressed in the NK cell lines YT and RNK 16, Because SLAM, the cell-surface protein with which SAP interacts, and 2B4, a membrane protein having sequence homologies with SLAM, also were found to be expressed on the surfaces of activated NK and T cell populations, they may access SAP functions in these populations. Whereas we found that 2B4 also binds SAP, 2B4-SAP interactions occurred only upon tyrosine phosphorylation of 2B4, By contrast, SLAM-SAP interactions were independent of phosphorylation of Y281 and Y327 on SLAM. As CD48, the ligand for 2B4, is expressed on the surface of Epstein-Barr virus (EBV)infected B cells, it is likely that SAP regulates signal transduction through this pair of cell-surface molecules. These data support the hypothesis that XLP is a result of both defective NK and T lymphocyte responses to EBV, The altered responses may be due to aberrant control of the signaling cascades which are initiated by the SLAM-SLAM and 2B4-CD48 interactions.