Falo L D, Benacerraf B, Rothstein L, Rock K L
Department of Pathology, Harvard Medical School, Boston, MA 02115.
J Immunol. 1987 Dec 15;139(12):3918-23.
Cerulenin is an antibiotic that inhibits eukaryotic lipid and sterol synthesis and blocks lipid modification of proteins. The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. This antibiotic strongly inhibits the ability of accessory cells to present antigen to murine T-T hybrids. This effect is observed for multiple distinct antigens including L-glutamic acid60-L-alanine30-L-tyrosine10, bovine insulin, L-glutamic acid56-L-lysine35-L-phenylalanine9, and ovalbumen. Presentation by both macrophage and B lymphoblastoid cell lines is inhibited. The ability to effectively pulse these cells with antigen is inhibited but not the ability of these same cells to present antigen that they have previously processed. Furthermore, this inhibition is selective as it can occur without significant inhibition of the antigen-presenting cell protein or DNA synthesis. Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. By these criteria this drug is shown to interfere with an antigen-processing step. The ability of cerulenin to block processing was compared with other known inhibitors. Although cerulenin was effective with all antigens tested, at least one inhibitor was not. Taken together, these results suggest that the effect of cerulenin may define a distinct step in antigen processing and provides evidence that some other processing events are not universally required. The ability of cerulenin to interfere with antigen processing is discussed in the context of the known actions of this antibiotic and events of antigen processing and presentation.
浅蓝菌素是一种抗生素，它能抑制真核生物的脂质和固醇合成，并阻断蛋白质的脂质修饰。研究了浅蓝菌素对辅助细胞向T细胞呈递抗原能力的影响。这种抗生素强烈抑制辅助细胞向小鼠T-T杂交细胞呈递抗原的能力。对于多种不同的抗原，包括L-谷氨酸60-L-丙氨酸30-L-酪氨酸10、牛胰岛素、L-谷氨酸56-L-赖氨酸35-L-苯丙氨酸9和卵清蛋白，都观察到了这种效果。巨噬细胞和B淋巴母细胞系的呈递均受到抑制。用抗原有效脉冲这些细胞的能力受到抑制，但这些相同细胞呈递它们先前处理过的抗原的能力不受影响。此外，这种抑制是选择性的，因为它可以在不显著抑制抗原呈递细胞蛋白质或DNA合成的情况下发生。用标记抗原评估，浅蓝菌素不抑制抗原摄取或分解代谢。根据这些标准，该药物被证明会干扰抗原处理步骤。将浅蓝菌素阻断处理的能力与其他已知抑制剂进行了比较。尽管浅蓝菌素对所有测试抗原都有效，但至少有一种抑制剂无效。综上所述，这些结果表明浅蓝菌素的作用可能定义了抗原处理中的一个独特步骤，并提供了证据表明一些其他处理事件并非普遍必需。在这种抗生素的已知作用以及抗原处理和呈递事件的背景下，讨论了浅蓝菌素干扰抗原处理的能力。
