Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants.
Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants.
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DOI：
10.4049/jimmunol.145.1.380
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发表时间：
1990-07
影响因子：
4.4
通讯作者：
H. Ljunggren;K. Sturmhöfel;E. Wolpert;G. Hämmerling;K. Kärre
中科院分区：
文献类型：
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作者：
H. Ljunggren;K. Sturmhöfel;E. Wolpert;G. Hämmerling;K. Kärre
YAC-1的β2-微球蛋白(β2M)缺陷型变种A.H-2-与基因组β2M克隆共转染。用转基因细胞研究β2M在干扰素诱导的NK细胞裂解中的作用。干扰素-γ治疗NK敏感的小鼠YAC-1淋巴瘤导致对NK细胞介导的裂解的敏感性降低，同时其固有的低MHC-I类表达增加。以前的研究表明，虽然A.H-2变异体保留了对干扰素-γ的其他反应，但它同时失去了这两种能力。在这里，β2m转基因恢复了YAC-1的表型，表现为诱导MHC I类分子的表达，并伴随着对干扰素-γ处理后的NK细胞裂解的保护。在没有干扰素-γ的情况下，转基因细胞的NK敏感性与A.H-2-没有显着差异。在体内传代的β2M转基因细胞中观察到了类似的对NK细胞裂解的保护作用，同时增强了MHC-I类分子的表达，而在体内传代的A.H-2-细胞中没有发现保护作用。本研究提供的证据表明，在YAC-1淋巴瘤中，干扰素-γ介导的NK细胞杀伤的保护作用依赖于β2M的表达。恢复MHC-I类分子的组装、运输以及伴随而来的干扰素-γ可增强的MHC-I类分子的细胞表面表达，可能是β2M效应的一个解释。
A beta 2-microglobulin (beta 2m)-deficient variant of YAC-1, A.H-2-, was transfected with a genomic beta 2m clone. Transfected cells were used to investigate the role of beta 2m in IFN-induced protection from NK cell lysis. IFN-gamma treatment of the NK-sensitive murine YAC-1 lymphoma results in reduced sensitivity to NK cell-mediated lysis in parallel with increased expression of its constitutively low MHC class I expression. It was previously shown that the A.H-2- variant had lost both these capacities, although it retained other responses to IFN-gamma. Here beta 2m transfection restored the YAC-1 phenotype with respect to an inducible expression of MHC class I molecules and a concomitant protection from NK cell lysis after treatment with IFN-gamma. In the absence of IFN-gamma the NK sensitivity of the transfectants did not differ significantly from A.H-2-. A similar protection from NK cell lysis, in parallel with enhanced MHC class I expression, was observed for in vivo-passaged beta 2m transfectants whereas no protection was found for in vivo-passaged A.H-2- cells. The present study provides evidence that the IFN-gamma-mediated protection from NK cell lysis is dependent on beta 2m expression in the YAC-1 lymphoma. Restoration of MHC class I assembly, transport, and concomitantly an IFN-gamma augmentable cell surface expression of MHC class I molecules is a possible explanation for the effect of beta 2m.