Oberg L, Eriksson M, Fahlén L, Sentman C L
Umeå Center for Molecular Pathogenesis, Umeå University, Sweden.
Eur J Immunol. 2000 Oct;30(10):2849-56. doi: 10.1002/1521-4141(200010)30:10<2849::AID-IMMU2849>3.0.CO;2-6.
In this study we investigated the balance between activating and inhibitory signals during T cell activation. We have used transgenic mice in which CD8+ T cells expressed an inhibitory receptor, Ly49A, and a specific activating alphabeta TCR. This TCR recognizes an lymphocytic choriomeningitis virus peptide in combination with H-2Db. We observed a quantitative influence on cellular responses that depended upon the activating signals received through the TCR and the inhibitory signals received through Ly49A. By varying the peptide concentration given to stimulating cells or target cells, we could adjust the amount of ligand available to trigger the TCR. At low doses of peptide, Ly49A-expressing T cells were unresponsive on target cells that expressed H-2Dd, but responded against target cells without H-2Dd. However, this inhibition could be overcome by increasing the peptide concentration or by addition of anti-Ly49A F(ab')2 fragments. Thus, rather than behaving as simple "off" switches, our data indicate that Ly49 receptors modulate T cell signaling so that higher amounts of activating signals are required for effector-cell responses.
在本研究中，我们调查了T细胞活化过程中激活信号与抑制信号之间的平衡。我们使用了转基因小鼠，其中CD8+ T细胞表达一种抑制性受体Ly49A和一种特异性激活的αβTCR。这种TCR与H-2Db结合识别淋巴细胞性脉络丛脑膜炎病毒肽。我们观察到对细胞反应的定量影响，这取决于通过TCR接收到的激活信号和通过Ly49A接收到的抑制信号。通过改变给予刺激细胞或靶细胞的肽浓度，我们可以调整可用于触发TCR的配体数量。在低剂量肽时，表达Ly49A的T细胞对表达H-2Dd的靶细胞无反应，但对无H-2Dd的靶细胞有反应。然而，这种抑制可以通过增加肽浓度或添加抗Ly49A F(ab')2片段来克服。因此，我们的数据表明Ly49受体并非简单地充当“关闭”开关，而是调节T细胞信号传导，使得效应细胞反应需要更高量的激活信号。
