DEMONSTRATION OF A NON-TAC PEPTIDE THAT BINDS INTERLEUKIN-2 - A POTENTIAL PARTICIPANT IN A MULTICHAIN INTERLEUKIN-2 RECEPTOR COMPLEX

DEMONSTRATION OF A NON-TAC PEPTIDE THAT BINDS INTERLEUKIN-2 - A POTENTIAL PARTICIPANT IN A MULTICHAIN INTERLEUKIN-2 RECEPTOR COMPLEX
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DOI:
10.1073/pnas.83.24.9694
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发表时间:
1986-12-01
影响因子:
11.1
通讯作者:
WALDMANN, TA
WALDMANN, TA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
TSUDO, M;KOZAK, RW;WALDMANN, TA

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白细胞介素-2(IL-2)受体系统在T细胞免疫应答中起关键作用。虽然IL-2结合被报道为仅限于Tac肽,但我们已经鉴定了不与抗人IL-2受体单克隆抗体反应的IL-2结合肽,所述抗人IL-2受体单克隆抗体包括在MLA 144(一种类人猿T细胞系)上的抗Tac。MLA 144细胞系每个细胞表达6800个IL-2结合位点,对人重组IL-2具有低亲和力(Kd = 14 nM)。使用交联方法,我们证明MLA 144上的IL-2结合肽比TAC肽大(Mr 75,000),TAC肽的Mr为55,000。除了Tac肽(Mr 54,000 - 57,000)外,还在Hut 102(一种人类T细胞嗜淋巴病毒I诱导的T细胞白血病细胞系)和植物血凝素激活的正常人类和巨猿淋巴母细胞上鉴定出了相似大小的IL-2结合肽(Mr 75,000)。抗Tac抗体不阻断125 I标记的IL-2与MLA 144细胞的结合。然而,该抗体不仅消除了125 I标记的IL-2与Hut 102细胞和正常淋巴母细胞上的Tac肽的结合,而且还消除了与Mr 75,000的IL-2结合肽的结合,这表明后一种肽与Tac肽结合形成高亲和力的IL-2受体复合物。
The interleukin-2 (IL-2) receptor system plays a key role in the T-cell immune response. Although IL-2 binding was reported to be restricted to the Tac peptide, we have identified an IL-2 binding peptide that does not react with anti-human IL-2 receptor monoclonal antibodies, including anti-Tac on MLA 144, a gibbon ape T-cell line. The MLA 144 cell line expressed 6800 IL-2 binding sites per cell with a low (Kd = 14 nM) affinity for human recombinant IL-2. Using cross-linking methodology, we demonstrated that the IL-2 binding peptide on MLA 144 is larger (Mr 75,000) than the TAC peptide, which has a Mr of 55,000. An IL-2 binding peptide of similar size (Mr 75,000) was also identified in addition to the Tac peptide (Mr 54,000-57,000) on Hut 102, a human T-cell lymphotrophic virus I-induced T-cell leukemia line, and phytohemagglutinin-activated normal human and gibbon ape lymphoblasts. Anti-Tac antibody did not block the binding of 125I-labeled IL-2 to MLA 144 cells. However, this antibody abolished the binding of 125I-labeled IL-2 not only to the Tac peptide on Hut 102 cells and normal lymphoblasts but also to the Mr 75,000 IL-2 binding peptide, suggesting that this latter peptide is associated with the Tac peptide to form the high-affinity IL-2 receptor complex.