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白细胞介素-2受体p55 + p75异二聚体复合物高亲和力白细胞介素-2结合位点形成的研究:单克隆抗体AHT-107所定义的p55亚基上一个决定簇的功能重要性

Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107.

作者信息

Osawa H, Diamantstein T

机构信息

Institut für Immunologie, Klinikum Steglitz, Freie Universität Berlin, Federal Republic of Germany.

出版信息

Immunol Lett. 1989 Feb;20(3):205-12. doi: 10.1016/0165-2478(89)90081-3.

DOI:10.1016/0165-2478(89)90081-3
PMID:2469650
Abstract

The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

单克隆抗体(mAb)AHT - 107识别位于人T淋巴母细胞白细胞介素2(IL - 2)受体(IL - 2R)p55亚基(Tac抗原,CD25)上IL - 2结合位点远端的一个决定簇,而mAb AHT - 54识别的决定簇靠近IL - 2结合位点,抗Tac抗体也是如此。AHT - 107抑制人T淋巴母细胞依赖IL - 2的增殖的效果与AHT - 54相同。两种单克隆抗体均抑制IL - 2与经福司可林处理的YT细胞上p55 + p75异二聚体复合物的高亲和力结合和交联。值得注意的是,AHT - 107不抑制IL - 2与人p55 cDNA转染细胞上p55分子的低亲和力结合和交联,而AHT - 54以及抗Tac抗体则会抑制。相反,先前报道的单克隆抗体PC61识别位于小鼠IL - 2R p55亚基上IL - 2结合位点远端的一个决定簇,并通过改变p55分子自身构象使IL - 2从高亲和力IL - 2R复合物上解离,它能抑制IL - 2与小鼠p55 cDNA转染细胞上p55分子的低亲和力结合和交联。此外,我们发现AHT - 107一旦在人T淋巴母细胞上形成高亲和力IL - 2R复合物后,不会使IL - 2从该复合物上解离。(摘要截短于250字)

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引用本文的文献

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Differential effects of a murine and chimeric mouse/human anti-interleukin-2 receptor antibody on human T-cell proliferation.鼠源及嵌合型鼠/人抗白细胞介素-2受体抗体对人T细胞增殖的不同作用
Immunology. 1992 Jul;76(3):452-9.