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白细胞介素2受体高亲和力复合物的逐步形成。

Stepwise formation of the high-affinity complex of the interleukin 2 receptor.

作者信息

Saito Y, Ogura T, Kamio M, Sabe H, Uchiyama T, Honjo T

机构信息

Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.

出版信息

Int Immunol. 1990;2(12):1167-77. doi: 10.1093/intimm/2.12.1167.

DOI:10.1093/intimm/2.12.1167
PMID:2090200
Abstract

The interleukin 2 receptor (IL-2R) is composed of at least two polypeptides--a 55 kd protein (the L chain, p55, or alpha chain) and a 75 kd protein (the H chain, p75 or beta chain). The high-affinity binding of IL-2 results in the formation of a ternary complex consisting of IL-2 and the L and H chains. We found that the rate of high-affinity complex formation at 0 degrees C was about one-third of that at 37 degrees C. The reduction of high-affinity complex formation rate at lower temperatures correlates with the reduction of lateral diffusion within the membrane at lower temperatures. An anti-H chain antibody (2RB) inhibited the formation of the high-affinity complex at 0 degrees C but not at 37 degrees C. We studied the kinetics of the high-affinity complex formation at 37 degrees C after the preincubation of ATL-2 cells with the 2RB antibody and IL-2 at 0 degrees C. We found that the amount of IL-2.L complex formed initially at 0 degrees C was almost equivalent to the amount of high-affinity complex formed by subsequent incubation at 37 degrees C. These results suggest that the IL-2.L complex might be converted to the high-affinity IL-2R complex. Similar experiments using YTC3 cells, which express a smaller number of L chains, showed slower rates of high-affinity complex formation, in agreement with the affinity conversion/stepwise binding model.

摘要

白细胞介素2受体(IL-2R)至少由两种多肽组成——一种55kd的蛋白质(L链,p55或α链)和一种75kd的蛋白质(H链,p75或β链)。IL-2的高亲和力结合导致形成由IL-2以及L链和H链组成的三元复合物。我们发现,0℃时高亲和力复合物的形成速率约为37℃时的三分之一。较低温度下高亲和力复合物形成速率的降低与较低温度下膜内横向扩散的减少相关。一种抗H链抗体(2RB)在0℃时抑制高亲和力复合物的形成,但在37℃时不抑制。我们研究了ATL-2细胞在0℃与2RB抗体和IL-2预孵育后在37℃时高亲和力复合物形成的动力学。我们发现,0℃时最初形成的IL-2.L复合物的量几乎等同于随后在37℃孵育形成的高亲和力复合物的量。这些结果表明,IL-2.L复合物可能会转化为高亲和力的IL-2R复合物。使用表达较少数量L链的YTC3细胞进行的类似实验显示,高亲和力复合物的形成速率较慢,这与亲和力转换/逐步结合模型一致。

相似文献

1
Stepwise formation of the high-affinity complex of the interleukin 2 receptor.白细胞介素2受体高亲和力复合物的逐步形成。
Int Immunol. 1990;2(12):1167-77. doi: 10.1093/intimm/2.12.1167.
2
Synergistic action of monoclonal antibodies directed at p55 and p75 chains of the human IL-2-receptor.针对人白细胞介素-2受体p55和p75链的单克隆抗体的协同作用。
J Immunol. 1991 Feb 1;146(3):884-92.
3
Role of alpha chain-IL-2 complex in the formation of the ternary complex of IL-2 and high-affinity IL-2 receptor.α链-白细胞介素-2复合物在白细胞介素-2与高亲和力白细胞介素-2受体三元复合物形成中的作用。
Int Immunol. 1990;2(6):521-30. doi: 10.1093/intimm/2.6.521.
4
A larger number of L chains (Tac) enhance the association rate of interleukin 2 to the high affinity site of the interleukin 2 receptor.大量的轻链(Tac)可提高白细胞介素2与白细胞介素2受体高亲和力位点的结合速率。
J Exp Med. 1988 Nov 1;168(5):1563-72. doi: 10.1084/jem.168.5.1563.
5
Why are multiple chains required for the interleukin 2 receptor?白细胞介素2受体为何需要多条链?
Prog Growth Factor Res. 1990;2(4):207-22. doi: 10.1016/0955-2235(90)90019-g.
6
The IL-2 receptor alpha-chain alters the binding of IL-2 to the beta-chain.白细胞介素-2受体α链改变白细胞介素-2与β链的结合。
J Immunol. 1991 Nov 15;147(10):3396-401.
7
Molecular mechanism for the formation of the high-affinity complex of interleukin 2 and its receptor.白细胞介素2与其受体高亲和力复合物形成的分子机制。
Mol Biol Med. 1988 Apr;5(2):123-38.
8
Evidence for p55-p75 heterodimers in the absence of IL-2 from Scatchard plot analysis.在没有白细胞介素-2的情况下,通过Scatchard图分析得到p55-p75异二聚体的证据。
Int Immunol. 1992 Jan;4(1):23-32. doi: 10.1093/intimm/4.1.23.
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Subunit structure of the high and low affinity human interleukin-15 receptors.人白细胞介素-15高亲和力和低亲和力受体的亚基结构。
Eur Cytokine Netw. 2000 Jun;11(2):207-15.
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Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R.白细胞介素2(IL-2)在体内激活的人自然杀伤细胞上表达的白细胞介素2受体(IL-2R)的特征:p64 IL-2Rγ链与功能性中等亲和力IL-2R中的IL-2Rβ链的关联。
J Exp Med. 1992 Aug 1;176(2):531-41. doi: 10.1084/jem.176.2.531.

引用本文的文献

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Mechanistic Models of Cellular Signaling, Cytokine Crosstalk, and Cell-Cell Communication in Immunology.免疫细胞信号转导、细胞因子串扰和细胞间通讯的机制模型。
Front Immunol. 2019 Sep 25;10:2268. doi: 10.3389/fimmu.2019.02268. eCollection 2019.
2
The effects of interleukin-2 on immune response regulation.白细胞介素-2对免疫反应调节的作用。
Math Med Biol. 2018 Mar 14;35(1):79-119. doi: 10.1093/imammb/dqw021.
3
Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: a fluorescence resonance energy transfer study.
白细胞介素2(IL-2)受体亚基在静息的Kit 225 K6 T细胞上的预组装及其受IL-2、IL-7和IL-15的调节:一项荧光共振能量转移研究。
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13134-9. doi: 10.1073/pnas.94.24.13134.
4
The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.白细胞介素(IL)-2受体β链为IL-2和一种细胞因子(暂命名为IL-T)所共有,IL-T可刺激T细胞增殖并诱导淋巴因子激活的杀伤细胞。
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4940-4. doi: 10.1073/pnas.91.11.4940.
5
Cooperative interactions between the interleukin 2 receptor alpha and beta chains alter the interleukin 2-binding affinity of the receptor subunits.白细胞介素2受体α链和β链之间的协同相互作用改变了受体亚基的白细胞介素2结合亲和力。
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3344-7. doi: 10.1073/pnas.91.8.3344.
6
T-helper functions in lines of mice selected for high or low antibody production (Selection III): modulation by anti-CD4+ monoclonal antibody.针对高或低抗体产生水平进行选择的品系小鼠(选择III)中的辅助性T细胞功能:抗CD4 +单克隆抗体的调节作用
Immunology. 1992 Jan;75(1):80-5.