Degen E, Laferté S, Elliott B E, Williams D B
Department of Biochemistry, University of Toronto, Ontario, Canada.
Int J Cancer. 1989 May 15;43(5):828-36. doi: 10.1002/ijc.2910430515.
Previous studies have shown that whereas a highly malignant mouse cell line termed MDAY-D2 (d haplotype) does not elicit a detectable response by cytotoxic T lymphocytes (CTL) in DBA/2 mice, strong anti-tumor CTL are generated against a wheat-germ-agglutinin-resistant variant, designated MDW3. Additional evidence suggests these anti-MDW3 CTL may not be a consequence of a unique antigenic determinant on the variant cells. Because MDW3 cells are expected to differ from MDAY-D2 cells in their surface carbohydrate structures (due to their lectin resistance) and Class I major histocompatibility molecules play a crucial role in CTL-mediated responses, we speculated that the Asn-linked oligosaccharides present on Class I molecules of MDAY-D2 and MDW3 might be different and could potentially influence recognition analyses and Con A-Sepharose affinity chromatography clearly demonstrated that the oligosaccharides isolated from the H-2Dd molecule of MDAY-D2 cells are larger and more highly branched than those of the MDW3 variant. Taken together with the finding that anti-MDW3 CTL are restricted by H-2Dd, these results suggested that the larger H-2Dd oligosaccharides on MDAY-D2 cells could potentially mask or perturb determinants required for recognition by these CTL. To test this postulate, the surface Class I oligosaccharides of both MDAY-D2 and MDW3 cells were converted to simpler hybrid structures by treatment with the oligosaccharide processing inhibitor, swainsonine. However, no effect was observed on the lysis or binding of either MDAY-D2 or MDW3 cells by anti-MDW3 CTL. Thus, the results do not support the possibility that the larger H-2Dd oligosaccharides on MDAY-D2 cells are, in themselves, responsible for the poor recognition of the parent tumor by anti-MDW3 CTL. Our data do indicate, however, that CTL target binding and effector functions are not dependent on the fine structure of complex Asn-linked carbohydrates present on Class I molecules and possibly on other, accessory molecules at the target cell surface, since MDW3 cells maintained their sensitivity to lysis by CTL following swainsonine treatment.
先前的研究表明,一种名为MDAY-D2(d单倍型)的高度恶性小鼠细胞系在DBA/2小鼠中不会引发细胞毒性T淋巴细胞(CTL)可检测到的反应,但针对一种名为MDW3的麦胚凝集素抗性变体可产生强烈的抗肿瘤CTL。其他证据表明,这些抗MDW3 CTL可能不是变体细胞上独特抗原决定簇的结果。由于MDW3细胞预计在其表面碳水化合物结构上与MDAY-D2细胞不同(因其凝集素抗性),且I类主要组织相容性分子在CTL介导的反应中起关键作用,我们推测MDAY-D2和MDW3的I类分子上存在的天冬酰胺连接的寡糖可能不同,并可能潜在地影响识别分析,伴刀豆球蛋白A-琼脂糖亲和层析清楚地表明,从MDAY-D2细胞的H-2Dd分子中分离出的寡糖比MDW3变体的更大且分支更多。结合抗MDW3 CTL受H-2Dd限制这一发现,这些结果表明MDAY-D2细胞上更大的H-2Dd寡糖可能潜在地掩盖或干扰这些CTL识别所需的决定簇。为了验证这一假设,用寡糖加工抑制剂苦马豆素处理MDAY-D2和MDW3细胞的表面I类寡糖,使其转化为更简单的杂合结构。然而,抗MDW3 CTL对MDAY-D2或MDW3细胞的裂解或结合均未观察到影响。因此,结果不支持MDAY-D2细胞上更大的H-2Dd寡糖本身导致抗MDW3 CTL对亲本肿瘤识别不佳的可能性。然而,我们的数据确实表明,CTL靶标结合和效应器功能不依赖于I类分子上存在的复杂天冬酰胺连接碳水化合物的精细结构,可能也不依赖于靶细胞表面的其他辅助分子,因为MDW3细胞在苦马豆素处理后仍保持对CTL裂解的敏感性。