Alternative splice variants of the human PD-1 gene

Alternative splice variants of the human PD-1 gene
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DOI:
10.1016/j.cellimm.2005.07.007
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发表时间:
2005-06-01
影响因子:
4.3
通讯作者:
Lillevang, ST
Lillevang, ST
中科院分区:
医学4区
文献类型:
--
作者:
Nielsen, C;Ohm-Laursen, L;Lillevang, ST

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PD-1是在活化的T细胞、B细胞和单核细胞的表面上表达的免疫调节受体。我们描述了四种选择性剪接的PD-1 mRNA转录物(PD- 1 Delta ex 2,PD-1 Delta ex 3,PD-1 Delta ex 2,3和PD-1 Delta ex 2,3,4)。PD-1 Delta ex 2和PD-1 Delta ex 3通过选择性剪接产生,其中外显子2(细胞外IgV样结构域)和外显子3(跨膜结构域)分别被剪接掉。因此,PD-1 Delta ex 3可能编码可溶性形式的PD-1。PD-1 Delta ex 2,3缺乏外显子2和3。这三种变体具有不受影响的开放阅读框架。PD-1 Delta ex 2、3、4缺乏外显子2、3和4(细胞内结构域),并在外显子5中含有提前终止密码子。用抗-CD 3+抗-CD 28单克隆抗体活化人PBMC可诱导每种PD-1转录物水平升高。活化后PD-1 Delta ex 3和flPD-1表达的平行增加表明推定的可溶性PD-1和flPD-1之间的重要相互作用可能涉及外周自身耐受性的维持和自身免疫的预防。(c)2005年爱思唯尔公司All rights reserved.
PD-1 is an immunoregulatory receptor expressed on the surface of activated T cells, B cells, and monocytes. We describe four alternatively spliced PD-1 mRNA transcripts (PD- 1 Delta ex2, PD-1 Delta ex3, PD-1 Delta ex2,3, and PD-1 Delta ex2,3,4) in addition to the full length isoform. PD-1 Delta ex2 and PD-1 Delta ex3 are generated by alternative splicing where exon 2 (extracellular IgV-Iike domain) and exon 3 (transmembrane domain) respectively are spliced out. PD-1 Delta ex3 is therefore likely to encode a soluble form of PD-1. PD-1 Delta ex2,3 lacks exon 2 and 3. These three variants have unaffected open reading frames. PD-1 Delta ex2, 3, 4 lacks exon 2, 3, and 4 (intracellular domain) and contains a premature stop codon in exon 5. Activation of human PBMCs with anti-CD3 + anti-CD28 monoclonal antibodies induces an increased level of each PD-1 transcript. A parallel increase in the expression of PD-1 Delta ex3 and flPD-1 upon activation suggests an important interplay between the putative soluble PD-1 and flPD-1 possibly involved in maintenance of peripheral self-tolerance and prevention of autoimmunity. (c) 2005 Elsevier Inc. All rights reserved.