Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1.

Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1.
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DOI:
10.1016/s0378-1119(01)00528-5
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发表时间:
2001-07
期刊:
影响因子:
3.5
通讯作者:
K. Yokota;A. Takashima;P. Bergstresser;K. Ariizumi
K. Yokota;A. Takashima;P. Bergstresser;K. Ariizumi
中科院分区:
生物学3区
文献类型:
--
作者:
K. Yokota;A. Takashima;P. Bergstresser;K. Ariizumi

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以前,我们确定了新的II型凝集素受体,dectin-1,这是优先表达的小鼠抗原呈递树突状细胞(DC),并参与DC的T细胞的共刺激。为了鉴定人同源物(DECTIN-1),我们采用从DC分离的mRNA的退化PCR扩增和随后的cDNA克隆。DECTIN-1是一种II型凝集素受体,与自然杀伤(NK)细胞表达的II型凝集素受体具有高度同源性。它在胞质结构域内含有基于免疫受体酪氨酸的激活基序。人DECTIN-1 mRNA主要由外周血白细胞表达,并优先由DC表达。mRNA可能编码33 kDa的糖蛋白。在人表皮中,该蛋白由朗格汉斯细胞选择性表达,朗格汉斯细胞是DC的表皮亚群。DECTIN-1 RNA的截短形式(称为Tβ)编码几乎缺乏整个颈部结构域的多肽,这是碳水化合物识别结构域与配体接近所必需的。基因组分析表明Tβ中缺失的氨基酸序列由一个外显子编码,表明Tβ RNA是通过选择性剪接产生的。DECTIN-1基因定位于12号染色体,位于p13.2和p12.3之间,靠近含有NK凝集素受体基因的NK基因复合体(12 p13.1至p13.2)。我们的研究结果表明,人类DECTIN-1与小鼠DECTIN-1有许多共同的特征,包括产生颈部结构域缺失的同种型,这可能下调DECTIN-1的共刺激功能。
Previously we identified the novel type II lectin receptor, dectin-1, that is expressed preferentially by murine antigen presenting dendritic cells (DC) and is involved in co-stimulation of T cells by DC. To identify the human homologue (DECTIN-1), we employed degenerative PCR amplification of mRNA isolated from DC and subsequent cDNA cloning. DECTIN-1 is a type II lectin receptor with high homology to type II lectin receptors expressed by natural killer (NK) cells. It contains an immunoreceptor tyrosine-based activation motif within the cytoplasmic domain. Human DECTIN-1 mRNA is expressed predominantly by peripheral blood leukocytes and preferentially by DC. The mRNA likely encodes a 33 kDa glycoprotein. In human epidermis, the protein is expressed selectively by Langerhans cells, which are an epidermal subset of DC. A truncated form of DECTIN-1 RNA (termed Tβ) encodes for a polypeptide lacking almost the entire neck domain, which is required for accessibility of the carbohydrate recognition domain to ligands. Genome analysis showed the deleted amino acid sequence in Tβ to be encoded by an exon, indicating that Tβ RNA is produced by alternative splicing. DECTIN-1 gene maps to chromosome 12, between p13.2 and p12.3, close to the NK gene complex (12p13.1 to p13.2) which contains genes for NK lectin receptors. Our results indicate that human DECTIN-1 shares many features with mouse dectin-1, including the generation of neck domain-lacking isoforms, which may down-regulate the co-stimulatory function of dectin-1.