Truman J P, Garban F, Choqueux C, Charron D, Mooney N
INSERM U396-Human Immunogenetics, Institut Biomédical des Cordeliers, Paris, France.
Exp Hematol. 1996 Oct;24(12):1409-15.
The class II human leucocyte antigens (HLA class II) are principally peptide presentation molecules. Signal transduction by these molecules has also been shown to transmit activation signals in both B and T lymphocytes by a pathway including protein tyrosine kinase activation, an intracellular calcium flux, and both the activation and transcriptional regulation of protein kinase C (PKC) isoforms. Apoptosis can also result from human leukocyte antigen class II stimulation. Inhibitors of gene transcription were used to inhibit activation and, therefore, to distinguish the signal transduction pathways important for apoptosis. This approach provided evidence that cellular activation and apoptosis undertook separate signaling pathways, and that PKC and intracellular calcium were shared between the two pathways, while tyrosine kinase activity was essential for cell activation. Further studies using cord blood B cells showed that these cells were incapable of generating a calcium flux after HLA class II ligation and were not subject to cell death. The importance of sustained levels of calcium for programmed cell death (PCD) was underlined since the restoration of a calcium flux enabled PCD of cord blood B cells via HLA class II. These results demonstrate that HLA class II stimulation initiates two distinct signal transduction pathways.
II类人类白细胞抗原（HLA - II类）主要是肽呈递分子。这些分子的信号转导也已显示通过一条包括蛋白酪氨酸激酶激活、细胞内钙流以及蛋白激酶C（PKC）同工型的激活和转录调控的途径，在B淋巴细胞和T淋巴细胞中传递激活信号。II类人类白细胞抗原刺激也可导致细胞凋亡。基因转录抑制剂被用于抑制激活，从而区分对细胞凋亡重要的信号转导途径。该方法提供了证据，表明细胞激活和细胞凋亡采用不同的信号转导途径，并且PKC和细胞内钙在这两条途径中是共享的，而酪氨酸激酶活性对细胞激活至关重要。使用脐血B细胞的进一步研究表明，这些细胞在II类HLA连接后不能产生钙流，并且不会发生细胞死亡。由于钙流的恢复使脐血B细胞通过II类HLA发生程序性细胞死亡（PCD），因此强调了持续水平的钙对程序性细胞死亡（PCD）的重要性。这些结果表明，II类HLA刺激启动了两条不同的信号转导途径。
