The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells
The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells
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DOI：
10.1002/eji.1830271230
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发表时间：
1997-12-01
影响因子：
5.4
通讯作者：
Grey, HM
中科院分区：
文献类型：
--
作者：
Kimachi, K;Croft, M;Grey, HM
尽管之前的研究表明，50-200个抗原主要组织相容性复合物（Ag-MHC）足以刺激MHC II类限制性T细胞杂交瘤显着分泌白细胞介素（IL）-2，但尚未对生理上更相关的T细胞群进行这种性质的研究。在这项研究中，我们分析了刺激来自 T 细胞受体 (TCR) 转基因动物的初始和先前引发的 T 细胞反应的配体需求，这些 TCR 特异于 I-E-k 呈递的鸽子细胞色素 c (PCC) 88-104 肽。引发的 T 细胞与之前报道的 T 细胞杂交瘤一样敏感，需要约 100 个 Ag-MHC 复合物才能合成易于检测数量的 IL-2，而初始 T 细胞需要 15 倍的配体才能产生等量的 IL-2。类似地，引发的 T 细胞需要大约 40 个 Ag-MHC 复合物才能产生显着的增殖反应，而初始 T 细胞需要大约 400 个复合物。与这些结果相反，在分析 T 细胞激活途径的早期事件时，初始 T 细胞和引发 T 细胞表现出相似的配体需求。即 TCR 下调、CD69 和 CD25 表达以及母细胞转化。对 IL-2 和 IL-2R 表达的进一步分析表明： 1) 在相同的配体浓度下，在引发的 T 细胞和初始 T 细胞中检测到 IL-2 的首次合成，但随着配体浓度的增加，引发的 T 细胞产生更多的 IL-2； 2) 尽管抗原剂量反应曲线相对于表达 IL-2R 的细胞百分比是相同的，但引发的 T 细胞表达的 IL-2 受体 (R) 比初始 T 细胞多约五倍。这些结果表明，初始 T 细胞和引发 T 细胞在启动 T 细胞激活所需的 Ag-MHC 复合物数量方面具有相同的阈值，但由于 IL-2 和 IL-2R 的低效表达，需要更多复合物的参与才能使初始 T 细胞合成必要量的这两种分子，从而使 T 细胞能够经历完整的复制周期。
Although previous studies have shown that 50-200 antigen-major histocompatibility complex complexes (Ag-MHC) are sufficient to stimulate significant secretion of interleukin (IL)-2 from MHC class II-restricted T cell hybridomas, there have been no studies of this nature on more physiologically relevant T cell populations. In this study we have analyzed the ligand requirements for stimulation of responses from naive and previously primed T cells derived from T cell receptor (TCR)-transgenic animals whose TCR is specific for the pigeon cytochrome c (PCC) 88-104 peptide presented by I-E-k. Primed T cells were as sensitive as the previously reported T cell hybridomas, requiring about 100 Ag-MHC complexes to synthesize readily detectable quantities of IL-2, whereas naive T cells required 15 times more ligand to produce equivalent quantities of IL-2. Similarly, primed T cells required about 40 Ag-MHC complexes to produce a significant proliferative response, whereas naive T cells required about 400 complexes. In contrast to these results, naive and primed T cells showed similar ligand requirements when early events in the T cell activation pathway were analyzed; i.e. TCR down-modulation, CD69 and CD25 expression, and blast transformation. A further analysis of IL-2 and IL-2R expression indicated: 1) The first synthesis of IL-2 was detected at the same ligand concentration in both primed and naive T cells, but primed T cells made much more IL-2 as the ligand concentrations increased; 2) primed T cells expressed about fivefold more IL-2 receptor (R) than naive T cells, despite the fact that the antigen dose-response curves with respect to the percentage of cells expressing IL-2R were identical. These results suggest that naive and primed T cells have the same threshold with respect to the number of Ag-MHC complexes required to initiate T cell activation, but that due to the inefficient expression of IL-2 and IL-2R, engagement of more complexes is needed to enable naive T cells to synthesize the necessary amounts of these two molecules to allow T cells to go through a complete cycle of replication.