Fibronectin binding protein A of Staphylococcus aureus can mediate human T lymphocyte adhesion and coactivation
Fibronectin binding protein A of Staphylococcus aureus can mediate human T lymphocyte adhesion and coactivation
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DOI：
10.4049/jimmunol.166.8.5129
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发表时间：
2001-04-15
影响因子：
4.4
通讯作者：
McIntyre, BW
中科院分区：
文献类型：
--
作者：
Miyamoto, YJ;Wann, ER;McIntyre, BW
细胞外基质蛋白纤连蛋白 (FN) 介导细菌和 T 淋巴细胞的粘附。哺乳动物细胞表达整合素 α (4)β (1) 和 α (5)β (1) 作为主要的 FN 结合细胞表面受体。金黄色葡萄球菌等细菌也表达 FN 结合受体，这对于粘附宿主组织和启动感染很重要。金黄色葡萄球菌 FN 结合蛋白 FnbpA 先前已被鉴定，并且已经制备了与该蛋白的不同功能区域相对应的重组蛋白。研究了三种重组截短形式的 FnbpA、rFnbpA(37-881)、rFnbpA(37-605) 和 rFnbpA(620-881) 对人 T 淋巴细胞体外粘附和共激活的影响。这些蛋白质与抗 CD3 mAb 共固定时，可激活 T 淋巴细胞增殖。 rFnbpA 蛋白产生的共激活信号需要含有含 FN 血清的培养基。此外，当 rFnbpAs 预载可溶性 FN 时，FN 耗尽的血清中的共刺激信号可以恢复。单克隆抗体阻断研究表明，整合素 α (5)β (1) 是负责 rFnbpA 共刺激信号的主要受体。剪切流细胞分离测定证实淋巴细胞可以与 rFnbpA 蛋白捕获的 FN 结合。这些结果表明，金黄色葡萄球菌 rFnbpA 可以通过 FN 桥与整合素 α (5)β (1) 相互作用，介导 T 淋巴细胞的粘附和共刺激信号。免疫学杂志，2001。
The extracellular matrix protein fibronectin (FN) mediates the adhesion of bacteria as well as T lymphocytes. Mammalian cells express integrins alpha (4)beta (1) and alpha (5)beta (1) as the major FN-binding cell surface receptors. Bacteria such as Staphylococcus aureas, also express FN-binding receptors that are important for adherence to host tissue and initiation of infection. The S. aureas FN-binding protein, FnbpA, has been previously identified, and recombinant proteins that correspond to distinct functional regions of this protein have been made. Three recombinant truncated forms of FnbpA, rFnbpA(37-881), rFnbpA(37-605), and rFnbpA(620-881), were examined for effects on in vitro adhesion and coactivation of human T lymphocytes. These proteins, when coimmobilized with anti-CD3 mAb, activated T lymphocyte proliferation. The coactivation signal generated by the rFnbpA proteins required medium containing serum with FN. Furthermore, the costimulatory signal could be restored in FN-depleted serum when the rFnbpAs were preloaded with soluble FN. Monoclonal Ab blocking studies revealed that integrin alpha (5)beta (1) is the major receptor responsible for the rFnbpA costimulatory signal. Shear flow cell detachment assays confirmed that lymphocytes can bind to FN captured by the rFnbpA proteins. These results suggest that the S. aureus rFnbpA can interact with integrin alpha (5)beta (1) via an FN bridge to mediate adhesion and costimulatory signals to T lymphocytes. The Journal of Immunology, 2001.