人白细胞抗原-G1对NK92效靶识别过程的影响
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生物膜与膜生物工程国家重点实验室资助项目.


Effects of Human Leukocyte Antigen-G1 on The Recognition of NK92 Effector-target Cells
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This work was supported by a grant from The National Key Laboratory of Biomembrane and Membrane Biotechnology.

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    摘要:

    人白细胞抗原G(human leukocyte antigen-G,HLA-G)属非经典的主要组织相容性复合体(major histocompatibility complex, MHC)Ⅰ类分子,为自然杀伤细胞(natural killer,NK)抑制性受体的识别配体,可以向NK细胞传递抑制性信号,从而抑制NK细胞的细胞毒作用.为了研究HLA-G对NK与靶细胞识别作用的影响机制,采用激光扫描共聚焦显微镜和流式细胞术对全长HLA-G1的表达和功能进行了探讨,并对效靶识别过程中靶细胞[Ca2+i(胞内自由钙离子浓度)进行了实时检测.结果发现,全长的HLA-G1表达于K562、JAR和CHO细胞的胞浆和胞膜上,它能够部分地抑制NK92的细胞毒作用. NK92与CHO和GFP-CHO细胞作用后,靶细胞[Ca2+i出现了明显的升高,HLA-G1的表达则抑制了靶细胞[Ca2+i的升高.结果提示:靶细胞[Ca2+i的升高是有效的细胞杀伤作用的必要条件,HLA-G的免疫抑制功能可能与靶细胞胞内钙离子浓度升高的抑制作用有密切关系.

    Abstract:

    Human leukocyte antigen-G(HLA-G) is a nonclassical major histocompatibility complex Ⅰ (MHC Ⅰ) molecule. As the ligand of NK inhibitor receptors, it can transmit the inhibitory signal and inhibit the cytotoxicity of NK cells. In order to study the effect of HLA-G1 on the recognition of effector-target cells, laser scanning confocal microscopy (LSCM) and flow cytometry were used to analyse the expression and function of full-length HLA-G1 and the real-time change of [Ca2+i (free intracellular Ca2+ concentration) in the target cells. Results showed that full-length HLA-G1 was expressed in the cytoplasm and on the cytomembrane of K562, JAR and CHO cells. HLA-G1 partially inhibited the cytotoxicity of NK92 in a 4h-51Cr-release assay. The [Ca2+i in the CHO and GFP-CHO (which expresses the green fluorescence protein) obviously rised after the addition of activated NK92. The expression of HLA-G1 inhibited this kind of rising. These results demonstrated that the rising of [Ca2+i in target cells is necessary for the effective cell cytotoxicity. The immune inhibition function of HLA-G1 is possible closely related to the inhibition of [Ca2+i in the target cells.

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田兴辉,周建军,方贞付,娄黎明,汪蕴,丰美福.人白细胞抗原-G1对NK92效靶识别过程的影响[J].生物化学与生物物理进展,2002,29(6):904-909

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  • 收稿日期:2002-04-10
  • 最后修改日期:2002-06-02
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