Identification of a membrane antigen that is distinct from the interleukin 2 receptor and that may be required for interleukin 2-driven proliferative responses.

Identification of a membrane antigen that is distinct from the interleukin 2 receptor and that may be required for interleukin 2-driven proliferative responses.
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鉴定与白细胞介素 2 受体不同且可能是白细胞介素 2 驱动的增殖反应所必需的膜抗原。

DOI:
10.4049/jimmunol.130.2.747
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发表时间:
1983
影响因子:
4.4
通讯作者:
E. Shevach
E. Shevach
中科院分区:
医学2区
文献类型:
--
作者:
T. Malek;R. Robb;E. Shevach

文献摘要

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在旨在培养针对豚鼠同种异体反应性 T 细胞系的鼠单克隆抗体的研究过程中,鉴定出一种 IgM 单克隆抗体 (5C3),它完全抑制免疫集落和具有不同抗原特异性的其他同种异体反应性 T 细胞集落的同种异体抗原和 IL 2 依赖性增殖反应。 FACS 上的组织分布表明,5C3 定义的表面抗原优先在有丝分裂原、同种异体抗原或抗原激活的 T 细胞上表达。 5C3 也是同种异体抗原和抗原诱导的 T 细胞增殖的有效抑制剂。此外,5C3显着抑制豚鼠Con A诱导的母细胞对含有豚鼠IL 2的培养液和部分纯化的人IL 2制剂的增殖反应,但对丝裂原诱导的T细胞增殖的抑制作用较差。在 5C3 存在的情况下,从肠系膜淋巴结细胞与 Con A 共培养获得的母细胞缺乏 5C3 定义的表面分子。然而,5C3-和5C3+母细胞群体吸收了等量的IL 2,这表明5C3-母细胞在IL 2受体的表达方面并不缺乏。然而,5C3-母细胞未能响应含有IL 2 的培养液而增殖。此外,5C3 对豚鼠 IL 2 受体与放射性标记的人 IL 2 的结合或随后的降解没有抑制活性。这些数据表明,5C3 识别与 IL 2 受体不同的推定 IL 2 受体效应物复合物的成分,并且该分子在 IL 2 传递至 T 淋巴细胞的生长信号的处理或生成中发挥关键作用。
During the course of studies designed to raise murine monoclonal antibodies to a guinea pig alloreactive T cell line, an IgM monoclonal antibody (5C3) was identified that completely inhibited the alloantigen and IL 2-dependent proliferative response of the immunizing colony and other alloreactive T cell colonies with different antigen specificities. Tissue distribution on the FACS demonstrated that the surface antigen defined by 5C3 was preferentially expressed on T cells activated by mitogen, alloantigen, or antigen. 5C3 was also a potent inhibitor of alloantigen- and antigen-induced T cell proliferation. In addition, 5C3 substantially inhibited the proliferative response of guinea pig Con A-induced blast cells to guinea pig IL 2-containing culture fluids and to a preparation of partially purified human IL 2 but was a poor inhibitor of mitogen-induced T cell proliferation. Blast cells obtained from the co-culture of mesenteric lymph node cells with Con A in the presence of 5C3 lacked the surface molecule defined by 5C3. The 5C3- and 5C3+ blast populations, nevertheless, absorbed equivalent amounts of IL 2, which suggested that 5C3- blasts were not deficient in the expression of IL 2 receptors. However, 5C3- blast cells failed to proliferate in response to IL 2-containing culture fluids. Furthermore, 5C3 had no inhibitory activity on either the binding or subsequent degradation of radiolabeled human IL 2 by guinea pig IL 2 receptors. These data suggest that 5C3 recognizes a component of a putative IL 2 receptor-effector complex distinct from the IL 2 receptor and that this molecule plays a critical role in the processing or generation of the growth signal IL 2 transmits to T lymphocytes.