KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals
KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals
复制标题
DOI：
10.1093/intimm/dxn013
复制
发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Witt, Campbell
中科院分区：
文献类型：
--
作者：
Foley, Bree;De Santis, Dianne;Witt, Campbell
NK细胞的细胞毒性通过激活和抑制信号的平衡来控制。同种异体反应性NK细胞的HLA特异性先前已显示由抑制性杀伤免疫球蛋白样受体（KIR）控制。同种异体反应性NK细胞裂解缺乏用于其抑制性KIR的HLA配体的靶标。我们已经详细描述了同种异体反应性NK克隆，其中特异性由活化受体KIR 2DS 1控制。仅表达HLA-C组2（C2）表位的靶细胞被该克隆裂解，并且纯合C2靶标比杂合C1/C2靶标裂解更强烈。抗CD 158 a（KIR 2DS 1）阻断了靶点的裂解，证实了KIR 2DS 1的作用。尽管该NK克隆表达NKG 2A（一种其配体为HLA-E的抑制性受体），但具有KIR 2DS 1和NKG 2A配体的靶标被该克隆裂解，表明KIR 2DS 1介导的激活信号优于NKG 2A介导的抑制信号。在来自缺乏C2表位的供体的多克隆扩增的NK培养物中，KIR 2DS 1活化的NK克隆占所有NK细胞的1%。这项研究强调了NK细胞在介导NK同种异体反应性中通过激活KIR控制的潜在作用。
NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for similar to 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.