Cutting edge:: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation

Cutting edge:: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation
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DOI:
10.4049/jimmunol.178.2.647
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发表时间:
2007-01-15
影响因子:
4.4
通讯作者:
Lanier, Lewis L.
Lanier, Lewis L.
中科院分区:
医学2区
文献类型:
--
作者:
Carr, William H.;Rosen, David B.;Lanier, Lewis L.

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杀伤细胞Ig样受体(M)基因KIR 3DS 1与减缓HIV感染的疾病进展有关;然而,对其表达、功能或配体特异性知之甚少。使用逆转录病毒转导的NKL细胞和来自KIR 3DS 1阳性供体的外周血NK细胞,我们通过流式细胞术评估了该基因的表达,并通过体外测定KIR 3DS 1诱导的细胞介导的细胞毒性和细胞因子产生来评估其功能。在本研究中,我们证明了KIR 3DS 1在外周血NK细胞上表达,并触发细胞毒性和IFN-γ产生。使用A共转染和免疫共沉淀,我们发现4,KIR 3DS 1与ITAM-轴承适配器,DAP 12。可溶性KIR 3DS 1-IG融合蛋白不与用HLA-Bw 4 80 I或80 T同种异型转染的EBV转化的B淋巴细胞系结合,表明如果KIR 3DS 1确实识别HLA-Bw 4配体,则这可能是肽依赖性的。
The killer cell Ig-like receptor (M) gene, KIR3DS1, has been implicated in slowing disease progression in HIV infection; however, little is known about its expression, function, or ligand specificity. Using retrovirally transduced NKL cells and peripheral blood NK cells from KIR3DS1-positive donors we assessed expression of this gene by flow cytometry and its function by in vitro assays measuring KIR3DS1-induced cell-mediated cytotoxicity and cytokine production. In the present study, we demonstrate that KIR3DS1 is expressed on peripheral blood NK cells and triggers both cytotoxicity and IFN-gamma production. Using A cotransfection and coimmunoprecipitation, we found 4 that KIR3DS1 associates with the ITAM-bearing adaptor, DAP12. Soluble KIR3DS1-Ig fusion proteins did not bind to EBV-transformed B lymphoid cell lines transfected with HLA-Bw4 80I or 80T allotypes, suggesting that if KIR3DS1 does recognize HLA-Bw4 ligands, this may be peptide dependent.