MOLECULAR-CLONING OF A LIGAND FOR THE INDUCIBLE T-CELL GENE 4-1BB - A MEMBER OF AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TUMOR-NECROSIS-FACTOR

MOLECULAR-CLONING OF A LIGAND FOR THE INDUCIBLE T-CELL GENE 4-1BB - A MEMBER OF AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TUMOR-NECROSIS-FACTOR
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DOI:
10.1002/eji.1830231037
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发表时间:
1993-10-01
影响因子:
5.4
通讯作者:
SMITH, CA
SMITH, CA
中科院分区:
医学3区
文献类型:
--
作者:
GOODWIN, RG;DIN, WS;SMITH, CA

文献摘要

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4-1BB是一种诱导型T细胞抗原,其序列与新兴的细胞因子受体家族成员具有同源性,包括肿瘤坏死因子和神经生长因子。为了帮助分析4-1BB的功能,我们利用该分子的可溶性形式作为探针来识别和克隆编码其配体的基因。4-1BB的配体是一种II型膜糖蛋白,与肿瘤坏死因子、淋巴毒素以及CD40和CD27的配体具有同源性,它们本身都是该超家族中受体的配体。4- 1bb基因位于小鼠4号染色体上,与肿瘤坏死因子受体的p80形式以及CD30基因接近。4-1BB配体基因定位于小鼠第17号染色体,但与肿瘤坏死因子和淋巴毒素基因相当远。4-1BB与其配体的相互作用诱导活化的胸腺细胞和脾T细胞的增殖,这一反应在4-1BB抗体刺激的类似细胞群上被模仿。
4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-1BB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-1BB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB.