Taniguchi M, Sakatsume M, Harada Y, Nores G A, Hakomori S
Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
Princess Takamatsu Symp. 1988;19:247-54.
Melanoma antigen was characterized by using the C57BL/6 mouse melanoma (B16) system, especially in relation to escape mechanisms of tumor cells from immunological surveillance. The antigen on the surface of melanoma cells selectively induced double negative cytotoxic T lymphocytes (CTL) lacking genetic restriction specificity in their action, whereas the soluble antigen shed or secreted from the cells preferentially induced suppressor T cells (Ts) inhibiting CTL generation in the induction phase. The epitopes of melanoma antigen for CTL and Ts were found to possess a "GM3-like structure". Anti-melanoma CTL activity was blocked by either GM3(NeuAc)-or GM3(NeuGc)-liposomes. Moreover, the GM3 (NeuGc)-liposome could induce anti-melanoma CTL when used as an antigen in the in vitro primary response. On the other hand, the soluble melanoma antigen or GM3(NeuAc)-but not GM3(NeuGc)-liposome itself specifically induced anti-melanoma Ts. Therefore, anti-melanoma Ts are able to distinguish GM3 molecular species. We also found two types of T cells, C3T4+ and double negative I-J+ T cells, to be involved in this suppression. Although the primary structure of melanoma GM3 was demonstrated to be the same as that of normal GM3, syngeneic anti-melanoma GM3 monoclonal antibody (M2590) did distinguish melanoma from normal cells. Further close analysis in liposome lysis experiments using various concentrations of GM3 clearly demonstrated that M2590 anti-melanoma GM3 only reacted with GM3 at a "high" density (more than 10-12 mol%), whereas no reactivity was observed at a "low" density (less than 7.5 mol%). It is clear, therefore, that the density of GM3 with normal primary structure is important in generating melanoma antigenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
通过使用C57BL/6小鼠黑色素瘤（B16）系统对黑色素瘤抗原进行了表征，特别是关于肿瘤细胞从免疫监视中逃逸的机制。黑色素瘤细胞表面的抗原选择性地诱导在作用中缺乏基因限制特异性的双阴性细胞毒性T淋巴细胞（CTL），而从细胞中脱落或分泌的可溶性抗原优先诱导抑制性T细胞（Ts），在诱导阶段抑制CTL的产生。发现针对CTL和Ts的黑色素瘤抗原表位具有“GM3样结构”。抗黑色素瘤CTL活性被GM3（NeuAc）-或GM3（NeuGc）-脂质体阻断。此外，GM3（NeuGc）-脂质体在体外初次反应中用作抗原时可诱导抗黑色素瘤CTL。另一方面，可溶性黑色素瘤抗原或GM3（NeuAc）-而非GM3（NeuGc）-脂质体本身特异性诱导抗黑色素瘤Ts。因此，抗黑色素瘤Ts能够区分GM3分子种类。我们还发现两种类型的T细胞，C3T4 +和双阴性I-J + T细胞参与了这种抑制作用。尽管黑色素瘤GM3的一级结构被证明与正常GM3相同，但同基因抗黑色素瘤GM3单克隆抗体（M25,90）确实能区分黑色素瘤细胞与正常细胞。在使用各种浓度GM3的脂质体裂解实验中的进一步仔细分析清楚地表明，M25,90抗黑色素瘤GM3仅在“高”密度（超过10-12 mol％）下与GM3反应，而在“低”密度（小于7.5 mol％）下未观察到反应性。因此，具有正常一级结构的GM3密度在产生黑色素瘤抗原性方面很重要。（摘要截断于250字）
