COEXPRESSION OF 2 DISTINCT GENES IS REQUIRED TO GENERATE SECRETED BIOACTIVE CYTOTOXIC LYMPHOCYTE MATURATION FACTOR
COEXPRESSION OF 2 DISTINCT GENES IS REQUIRED TO GENERATE SECRETED BIOACTIVE CYTOTOXIC LYMPHOCYTE MATURATION FACTOR
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DOI：
10.1073/pnas.88.10.4143
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
GATELY, MK
中科院分区：
文献类型：
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作者：
GUBLER, U;CHUA, AO;GATELY, MK
细胞毒性淋巴细胞成熟因子(CLMF)是一种二硫键结合的异二聚体淋巴因子，它(1)作为T细胞的生长因子，不依赖于白介素2(IL-2)；(2)与亚适浓度的白介素2协同诱导淋巴因子激活的杀伤细胞。我们现在报道从淋巴母细胞B细胞系NC-37中克隆和表达两个人CLMF亚单位的cDNA。这两个亚基代表两个截然不同且不相关的基因产物，它们的mRNAs在NC-37细胞激活时被协同诱导。这两个亚单位在COS细胞中的共表达是分泌具有生物活性的CLMF所必需的；单独转染其中一个亚单位的COS细胞不能分泌具有生物活性的CLMF。在哺乳动物细胞中表达的重组CLMF具有与天然CLMF基本相同的生物学活性，其活性可被天然CLMF的单抗所中和。由于这种异源二聚体蛋白表现出白介素12的特性，我们建议将CLMF命名为白介素12。
Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of interleukin 2 to induce lymphokine-activated killer cells. We now report the cloning and expression of both human CLMF subunit cDNAs from a lymphoblastoid B-cell line, NC-37. The two subunits represent two distinct and unrelated gene products whose mRNAs are coordinately induced upon activation of NC-37 cells. Coexpression of the two subunit cDNAs in COS cells is necessary for the secretion of biologically active CLMF; COS cells transfected with either subunit cDNA alone do not secrete bioactive CLMF. Recombinant CLMF expressed in mammalian cells displays biologic activities essentially identical to natural CLMF, and its activities can be neutralized by monoclonal antibodies prepared against natural CLMF. Since this heterodimeric protein displays the properties of an interleukin, we propose that CLMF be given the designation interleukin 12.