Hirabayashi Y, Taniguchi M
Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Science, Japan.
Hum Cell. 1989 Mar;2(1):63-9.
We have shown that a syngenic monoclonal antibody, M2590, established after immunization of C57BL/6 mice with B16 melanoma cells, recognized GM3 (NeuAc) ganglioside. Although GM3 is widely distributed among various normal cells and tissues, the antibody did not react with them. However, it reacted exclusively with melanoma cells from mouse, hamster and human. Preliminary experiments suggested that proteins and lipids as well as GM3 density on B16 cells are involved in the reactivity of GM3 with the antibody. Then, we investigated the biological function of the melanoma antigen, which was secreted from B16 cells into the culture medium. This soluble antigen was shown to suppress the positive immune responses by inhibiting CTL activity in the effector phase and by induction of specific suppressor T cells (Ts) that block CTL generation in the induction phase. Liposomes containing GM3 (NeuAc) but not GM3 (NeuGc) can effectively induce the melanoma specific Ts as did the soluble antigen. The results indicated the tumor cells can escape from host-immune system by stimulating the repertoire of Ts for self-antigen, GM3. To understand the biological role of GM3, we have established mutant clones of no-expressor of GM3 recognized by M2590. The clones were found to have lower attachment to laminin and type IV collagen and poor ability of lung metastasis.
我们已经证明，在用B16黑色素瘤细胞免疫C57BL/6小鼠后建立的同基因单克隆抗体M2590可识别GM3（NeuAc）神经节苷脂。尽管GM3广泛分布于各种正常细胞和组织中，但该抗体与它们不发生反应。然而，它仅与来自小鼠、仓鼠和人类的黑色素瘤细胞发生反应。初步实验表明，B16细胞上的蛋白质、脂质以及GM3密度与GM3和该抗体的反应性有关。然后，我们研究了从B16细胞分泌到培养基中的黑色素瘤抗原的生物学功能。这种可溶性抗原被证明可通过在效应阶段抑制CTL活性以及在诱导阶段诱导阻断CTL生成的特异性抑制性T细胞（Ts）来抑制阳性免疫反应。含有GM3（NeuAc）而非GM3（NeuGc）的脂质体能够像可溶性抗原一样有效地诱导黑色素瘤特异性Ts。结果表明，肿瘤细胞可通过刺激针对自身抗原GM3的Ts库来逃避宿主免疫系统。为了解GM3的生物学作用，我们建立了不表达M2590所识别的GM3的突变克隆。发现这些克隆对层粘连蛋白和IV型胶原的附着性较低，肺转移能力也较差。
