Jensen P E
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322.
J Immunol. 1988 Oct 15;141(8):2545-50.
Recent studies indicate that Ag pass through a chloroquine-sensitive intracellular pathway in accessory cells before they are recognized by class II-restricted T cells. Our results indicate that this is also true for insulin. Unexpectedly, we find that protein synthesis is required for optimal accessory cell-dependent processing of insulin and other proteins by adherent macrophages. Treatment of APC with inhibitors of protein synthesis, before and during exposure to Ag, inhibits their subsequent ability to activate murine T cell hybridomas. Experiments are described which suggest that this effect is localized to intracellular processing of Ag rather than uptake or presentation, per se. Inhibition is reversible, and is not observed in special situations where intracellular processing of Ag is not required. A distinct lag period is required for inhibition of processing after inhibition of macrophage protein synthesis. One possible interpretation is that protein synthesis is necessary for maintenance of a labile protein crucial for intracellular processing of Ag. Alternatively, the susceptibility of processing to inhibitors of protein synthesis may reflect an obligate intracellular association of Ag and newly synthesized class II histocompatibility molecules.
最近的研究表明，抗原在被Ⅱ类限制性T细胞识别之前，通过辅助细胞中一条对氯喹敏感的细胞内途径。我们的结果表明胰岛素也是如此。出乎意料的是，我们发现蛋白质合成对于黏附巨噬细胞对胰岛素及其他蛋白质进行最佳的辅助细胞依赖性加工是必需的。在抗原暴露之前及期间，用蛋白质合成抑制剂处理抗原呈递细胞（APC），会抑制其随后激活小鼠T细胞杂交瘤的能力。所描述的实验表明，这种效应局限于抗原的细胞内加工过程，而非摄取或呈递本身。抑制是可逆的，并且在不需要抗原细胞内加工的特殊情况下未观察到。巨噬细胞蛋白质合成被抑制后，抑制加工需要一个明显的延迟期。一种可能的解释是，蛋白质合成对于维持一种对抗原细胞内加工至关重要的不稳定蛋白质是必要的。或者，加工过程对蛋白质合成抑制剂的敏感性可能反映了抗原与新合成的Ⅱ类组织相容性分子之间必然的细胞内关联。
