Gómez-Lozano Natalia, Estefanía Ernesto, Williams Fionnuala, Halfpenny Iris, Middleton Derek, Solís Rosario, Vilches Carlos
Servicio de Inmunología, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Eur J Immunol. 2005 Jan;35(1):16-24. doi: 10.1002/eji.200425493.
Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse, and enable human NK cells to survey the expression of individual HLA class I molecules, often altered in infections and tumors. Multiple events of non-reciprocal recombination have contributed to the rapid diversification of KIR. We show that approximately 4.5% of the individuals of a Caucasoid population bear a recombinant allele of KIR3DP1, officially designed KIR3DP1004, that associates tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1. The KIR3DP1 gene is normally silent, but the recombinant allele carries a novel promoter sequence and, as a consequence, is transcribed in all tested individuals. Messenger RNA of KIR3DP1004 is made up of six exons; of these, exons 1-5 are similar to, and spliced like, those encoding the leader peptide and Ig-domains of KIR3D. By contrast, exon 6 is homologous to no other human KIR sequence, but only to possible homologs in chimpanzees and rhesus macaques, and encodes a short hydrophilic tail. The putative KIR3DP1*004 product, like those of the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the extracellular medium rather than anchored to the cell membrane.
杀伤细胞免疫球蛋白样受体（KIR）在结构和功能上具有多样性，使人类自然杀伤细胞（NK细胞）能够监测个体人类白细胞抗原I类分子（HLA-I）的表达情况，而这种表达在感染和肿瘤中常常发生改变。多次非相互重组事件促使KIR快速多样化。我们发现，在一个高加索人群中，约4.5%的个体携带KIR3DP1的重组等位基因，官方命名为KIR3DP1004，它与KIR3DP1、KIR2DL4以及KIR3DL1/KIR3DS1的基因重复紧密相关。KIR3DP1基因通常处于沉默状态，但该重组等位基因携带一个新的启动子序列，因此在所有检测个体中都能转录。KIR3DP1004的信使核糖核酸由六个外显子组成；其中，外显子1至5与编码KIR3D前导肽和免疫球蛋白结构域的外显子相似，且剪接方式相同。相比之下，外显子6与其他人类KIR序列均无同源性，仅与黑猩猩和恒河猴中可能的同源序列有同源性，并且编码一个短的亲水性尾巴。推测的KIR3DP1*004产物，与相关基因LAIR-2和LILRA3/ILT6/LIR4的产物一样，预计会分泌到细胞外介质中，而不是锚定在细胞膜上。
