NATURAL-KILLER SUSCEPTIBILITY OF HUMAN-CELLS MAY BE REGULATED BY GENES IN THE HLA REGION ON CHROMOSOME-6
NATURAL-KILLER SUSCEPTIBILITY OF HUMAN-CELLS MAY BE REGULATED BY GENES IN THE HLA REGION ON CHROMOSOME-6
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DOI：
10.1073/pnas.83.15.5688
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发表时间：
1986-08-01
影响因子：
11.1
通讯作者：
FRADELIZI, D
中科院分区：
文献类型：
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作者：
HARELBELLAN, A;QUILLET, A;FRADELIZI, D
在没有任何有意免疫的情况下，自然杀伤（NK）细胞存在于每个个体中。它们能够杀死多种肿瘤和正常来源的靶标。然而，它们的确切生理作用尚不清楚。在这项研究中，我们报告了人类 Epstein-Barr 病毒转化的 B 细胞系的结果，该细胞系衍生出了扰乱 HLA 分子表达的变体。我们的结果表明，在这些细胞系中，HLA 抗原的表达与 NK 裂解的易感性之间存在反比关系。原始细胞系对 NK 裂解具有高度抵抗力。相反，I类抗原表达受到干扰的变体是高度敏感的。 II 类抗原表达受到干扰的变异体的敏感性为中等。干扰素可在不相关的经典 K-562 靶细胞中诱导 HLA I 类表达和 NK 抗性，但不会改变变异细胞系中的 HLA 表达或 NK 敏感性。原始细胞系和变体之间的差异并不在于被 NK 效应子结合的能力。我们的结果表明 HLA 分子具有不同的作用。通过此处讨论的某种未知机制，细胞表面 HLA 分子的存在将防止该细胞被 NK 细胞杀死。这种“健康状况良好”信号的丧失将导致细胞通过 NK 裂解而被消灭。
Natural killer (NK) cells exist in each individual in the absence of any intentional immunization. They are able to kill a wide range of targets from tumoral as well as from normal origin. However, their exact physiologic role is not clearly understood. In this study we report results about a human Epstein-Barr virus-transformed B-cell line from which variants perturbed in the expression of HLA molecules have been derived. Our results indicate that in these cell lines an inverse relationship exists between expression of HLA antigens and susceptibility to NK lysis. The original cell line is highly resistant to NK lysis. On the contrary, the variant perturbed in class I antigen expression is highly susceptible. Variant perturbed in class II antigen expression is intermediate in susceptibility. Interferon, which induces HLA class I expression and NK resistance in the unrelated classical K-562 target cells, does not change either HLA expression or NK susceptibility in the variant cell lines. The difference between the original cell line and the variants does not reside in the ability to be bound by NK effectors. Our results suggest a different role for HLA molecules. By some unknown mechanism discussed here, the presence of HLA molecules at the surface of a cell would prevent this cell from being killed by NK cells. The loss of this "good health" signal would lead to the elimination of the cell through NK lysis.