Division of Immunology, Department of Pathology, University of Cambridge, UK.
Eur J Immunol. 2009 Nov;39(11):3195-206. doi: 10.1002/eji.200839080.
Leucocyte Ig-like receptors (LILR) are a family of innate immune receptors expressed on myeloid and lymphoid cells that influence adaptive immune responses. We identified a common mechanism of alternative mRNA splicing, which generates transcripts that encode soluble protein isoforms of the majority of human LILR. These alternative splice variants lack transmembrane and cytoplasmic encoding regions, due to the transcription of a cryptic stop codon present in an intron 5' of the transmembrane encoding exon. The alternative LILR transcripts were detected in cell types that express their membrane-associated isoforms. Expression of the alternative LILRB1 transcript in transfected cells resulted in the release of a soluble approximately 65 Kd LILRB1 protein into culture supernatants. Soluble LILRB1 protein was also detected in the culture supernatants of monocyte-derived DC. In vitro assays suggested that soluble LILRB1 could block the interaction between membrane-associated LILRB1 and HLA-class I. Soluble LILRB1 may act as a dominant negative regulator of HLA-class I-mediated LILRB1 inhibition. Soluble isoforms of the other LILR may function in a comparable way.
白细胞免疫球蛋白样受体（LILR）是一类表达于髓系和淋巴系细胞的固有免疫受体，影响适应性免疫反应。我们发现了一种常见的可变剪接机制，该机制产生的转录本编码大多数人 LILR 的可溶性蛋白同工型。这些可变剪接变体由于跨膜编码外显子 5' 内含子中存在的隐藏终止密码子的转录，缺乏跨膜和细胞质编码区。在表达其膜相关同工型的细胞类型中检测到了可变剪接的 LILR 转录本。在转染细胞中表达可变剪接的 LILRB1 转录本会导致可溶性约 65 Kd LILRB1 蛋白释放到培养上清液中。单核细胞衍生的 DC 的培养上清液中也检测到可溶性 LILRB1 蛋白。体外测定表明，可溶性 LILRB1 可阻断膜相关 LILRB1 与 HLA 类 I 之间的相互作用。可溶性 LILRB1 可能作为 HLA 类 I 介导的 LILRB1 抑制的显性负调节剂发挥作用。其他 LILR 的可溶性同工型可能以类似的方式发挥作用。
