Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.
Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.
复制标题
DOI：
10.1038/ni.3513
复制
发表时间：
2016-09
影响因子：
30.5
通讯作者：
Altfeld M
中科院分区：
文献类型：
--
作者：
Garcia-Beltran WF;Hölzemer A;Martrus G;Chung AW;Pacheco Y;Simoneau CR;Rucevic M;Lamothe-Molina PA;Pertel T;Kim TE;Dugan H;Alter G;Dechanet-Merville J;Jost S;Carrington M;Altfeld M
活化NK细胞受体KIR 3DS 1与多种人类疾病的结果有关，包括延迟的HIV-1疾病进展，但导致其生物学效应的配体仍然未知。我们筛选了100种HLA-I蛋白，发现KIR 3DS 1结合HLA-F，这在生物化学和功能上都得到了验证。原代人KIR 3DS 1 + NK细胞在遇到HLA-F时脱颗粒并产生抗病毒细胞因子，并在体外抑制HIV-1复制。CD 4 + T细胞活化触发HLA-F转录和表达并诱导KIR 3DS 1配体表达。HIV-1感染进一步增加HLA-F转录，但降低KIR 3DS 1配体表达，表明免疫逃避机制。总之，我们建立了HLA-F作为KIR 3DS 1的配体，并证明了HLA-F的细胞环境依赖性表达，这可能解释了KIR 3DS 1在人类疾病中的广泛影响。
The activating NK-cell receptor KIR3DS1 has been implicated in the outcome of various human diseases, including delayed HIV-1 disease progression, yet a ligand that accounts for its biological effects remained unknown. We screened 100 HLA-I proteins and found that KIR3DS1 binds HLA-F, which was validated biochemically and functionally. Primary human KIR3DS1+ NK cells degranulated and produced antiviral cytokines upon encountering HLA-F, and inhibited HIV-1 replication in vitro. CD4+ T-cell activation triggered HLA-F transcription and expression and induced KIR3DS1 ligand expression. HIV-1 infection further increased HLA-F transcription, but decreased KIR3DS1 ligand expression, indicating an immune-evasion mechanism. Altogether, we established HLA-F as a ligand of KIR3DS1, and demonstrated cell-context-dependent expression of HLA-F that may explain the widespread influence of KIR3DS1 in human diseases.