Lampson L A, Fisher C A
Proc Natl Acad Sci U S A. 1984 Oct;81(20):6476-80. doi: 10.1073/pnas.81.20.6476.
Previous work showed that each of four human neuronal cell lines expresses less than or equal to 0.5% of the HLA-A,B,C and beta 2-microglobulin seen in glial, lymphoid, and other cell types, and there is a corresponding weak expression in neuroblastoma tumor and adult brain. Here, we probe the genetic basis of this weak expression. For each of three neuroblastoma cell lines, we show that HLA-A,B,C and beta 2-microglobulin can be induced by interferon and that the induction occurs within every cell of the population. Class II (Ia) molecules are not detected. Microscopic assay and radioimmunoassay of intact cells suggest that the induced antigen appears at the cell surface as well as within each cell. Immunoblot analysis confirms that the induced proteins have the structure of class I molecules. Thus, the normal weak HLA and beta 2-microglobulin expression of these cell lines appears to reflect a regulatory control rather than a primary genetic lesion. According to current theory, lack of HLA-A,B,C should protect transformed, infected, or damaged neurons--but also neurons in neural transplants--from T-cell-mediated immunosurveillance. The possibility that neuronal HLA-A,B,C expression may be under regulatory control is of importance in this context.
先前的研究表明,四种人类神经元细胞系中的每一种所表达的HLA - A、B、C以及β2 - 微球蛋白,都少于或等同于在神经胶质细胞、淋巴细胞及其他细胞类型中所观察到的0.5%,并且在神经母细胞瘤肿瘤和成人脑中存在相应的弱表达。在此,我们探究这种弱表达的遗传基础。对于三种神经母细胞瘤细胞系中的每一种,我们都发现HLA - A、B、C以及β2 - 微球蛋白可被干扰素诱导,并且诱导发生在群体中的每个细胞内。未检测到II类(Ia)分子。对完整细胞的显微镜检测和放射免疫分析表明,诱导的抗原出现在细胞表面以及每个细胞内部。免疫印迹分析证实,诱导的蛋白质具有I类分子的结构。因此,这些细胞系正常的弱HLA和β2 - 微球蛋白表达似乎反映的是一种调控控制,而非原发性遗传损伤。根据当前理论,缺乏HLA - A、B、C应能保护转化的、受感染的或受损的神经元——以及神经移植中的神经元——免受T细胞介导的免疫监视。在这种情况下,神经元HLA - A、B、C表达可能受调控控制这一可能性具有重要意义。