Cerundolo V, Benham A, Braud V, Mukherjee S, Gould K, Macino B, Neefjes J, Townsend A
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
Eur J Immunol. 1997 Jan;27(1):336-41. doi: 10.1002/eji.1830270148.
We describe the effect of the proteasome specific inhibitor lactacystin on the metabolic stability of influenza nucleoprotein (NP) and on the generation of antigens presented by human and murine class I molecules of the major histocompatibility complex to cytotoxic T lymphocytes (CTL). We show that cells treated with lactacystin fail to present influenza antigens to influenza-specific CTL, but retain the capacity to present defined epitopes expressed as peptides intracellularly by recombinant vaccinia viruses. This block in antigen presentation can be overcome by expressing the viral protein within the lumen of the endoplasmic reticulum, confirming the specificity of lactacystin for cytosolic proteases. We also show that the effect of lactacystin on antigen presentation correlates with the block of breakdown of a rapidly degraded form of the influenza NP linked to ubiquitin. These results demonstrate that proteasome-dependent degradation plays an important role in the cytosolic generation of CTL epitopes.
我们描述了蛋白酶体特异性抑制剂乳胞素对流感核蛋白（NP）代谢稳定性以及对主要组织相容性复合体的人和鼠类I类分子呈递给细胞毒性T淋巴细胞（CTL）的抗原产生的影响。我们发现，用乳胞素处理的细胞无法将流感抗原呈递给流感特异性CTL，但保留了呈递由重组痘苗病毒在细胞内表达为肽的特定表位的能力。通过在内质网腔中表达病毒蛋白可以克服这种抗原呈递障碍，这证实了乳胞素对胞质蛋白酶的特异性。我们还表明，乳胞素对抗原呈递的影响与与泛素相连的流感NP快速降解形式的降解受阻相关。这些结果表明，蛋白酶体依赖性降解在CTL表位的胞质产生中起重要作用。
