Enhanced interaction between SEC2 mutant and TCR V induces MHC II-independent activation of T cells via PKC/NF-B and IL-2R/STAT5 signaling pathways
文献类型：期刊论文
| 作者 | Fu, Xuanhe1,2; Xu, Mingkai1; Song, Yubo1; Li, Yongqiang1; Zhang, Huiwen1; Zhang, Jinghai2; Zhang, Chenggang1 |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2018-12-21 |
| 卷号 | 293期号:51页码:19771-19784 |
| ISSN号 | 0021-9258 |
| 关键词 | interleukin NF-B (NF-KB) STAT transcription factor signaling signal transduction IL-2 staphylococcal enterotoxin C2 superantigen T-cell receptor T-cell activation |
| DOI | 10.1074/jbc.RA118.003668 |
| 英文摘要 | SEC2, a major histocompatibility complex class II (MHC II)-dependent T-cell mitogen, binds MHC II and T-cell receptor (TCR) Vs to induce effective co-stimulating signals for clonal T-cell expansion. We previously characterized a SEC2 mutant with increased recognition of TCR Vs, ST-4, which could intensify NF-B signaling transduction, leading to IL-2 production and T-cell activation. In this study, we found that in contrast to SEC2, ST-4 could induce murine CD4(+) T-cell proliferation in a V8.2- and V8.3-specific manner in the absence of MHC II+ antigen-presenting cells (APCs). Furthermore, although IL-2 secretion in response to either SEC2 or ST-4 stimulation was accompanied by up-regulation of protein kinase C (PKC), inhibitor of B (IB), and IB kinase (IKK/), IB, and NF-B in mouse splenocytes, only ST-4 could activate CD4(+) T cells in the absence of MHC II+ APCs through the PKC/NF-B signaling pathway. The PKC inhibitor AEB071 significantly suppressed SEC2/ST-4-induced T-cell proliferation, CD69 and CD25 expression, and IL-2 secretion with or without MHC II+ APCs. Further, SEC2/ST-4-induced changes in PKC/NF-B signaling were significantly relieved by AEB071 in a dose-dependent manner. Using Lck siRNA, we found that Lck controlled SEC2/ST-4-induced phosphorylation of PKC. We also demonstrated that the IL-2R/STAT5 pathway is essential for SEC2/ST-4-induced T-cell activation. Collectively, our data demonstrate that an enhanced ST-4-TCR interaction can compensate for lack of MHC II and stimulate MHC II-free CD4(+) T-cell proliferation via PKC/NF-B and IL-2R/STAT5 signaling pathways. Compared with SEC2, intensified PKC/NF-B and IL-2R/STAT5 signals induced by ST-4 lead to enhanced T-cell activation. The results of this study will facilitate better understanding of TCR-based immunotherapies for cancer. |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences Grant[XDA12020225] ; Science and Technology Plan Projects of Shenyang City[Z17-7-013] ; Science and Technology Plan Projects of Shenyang City[Y17-4-003] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| WOS记录号 | WOS:000454294900022 |
| 源URL | [http://210.72.129.5/handle/321005/123843]  |
| 专题 | 中国科学院沈阳应用生态研究所 |
| 通讯作者 | Xu, Mingkai; Zhang, Jinghai |
| 作者单位 | 1.Chinese Acad Sci, Inst Appl Ecol, 72 WenHua Rd, Shenyang 110016, Liaoning, Peoples R China 2.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, 103 WenHua Rd, Shenyang 110016, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fu, Xuanhe,Xu, Mingkai,Song, Yubo,et al. Enhanced interaction between SEC2 mutant and TCR V induces MHC II-independent activation of T cells via PKC/NF-B and IL-2R/STAT5 signaling pathways[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(51):19771-19784. |
| APA | Fu, Xuanhe.,Xu, Mingkai.,Song, Yubo.,Li, Yongqiang.,Zhang, Huiwen.,...&Zhang, Chenggang.(2018).Enhanced interaction between SEC2 mutant and TCR V induces MHC II-independent activation of T cells via PKC/NF-B and IL-2R/STAT5 signaling pathways.JOURNAL OF BIOLOGICAL CHEMISTRY,293(51),19771-19784. |
| MLA | Fu, Xuanhe,et al."Enhanced interaction between SEC2 mutant and TCR V induces MHC II-independent activation of T cells via PKC/NF-B and IL-2R/STAT5 signaling pathways".JOURNAL OF BIOLOGICAL CHEMISTRY 293.51(2018):19771-19784. |
入库方式： OAI收割
来源：沈阳应用生态研究所
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