Goth S, Nguyen V, Shastri N
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
J Immunol. 1996 Sep 1;157(5):1894-904.
Proteolysis of endogenously synthesized cellular proteins is essential for constitutive display of processed peptide/MHC class I complexes on the APC surface for stimulating CD8+ T cells. However, the extent to which normal protein turnover serves as the source of processed peptides is not clear. To address this question, we used pairs of novel N-end rule substrates that varied in their intracellular stability and served as precursors for generating peptide/MHC class I (OVA257-264/Kb or influenza nucleoprotein 366-374/Db) complexes. Surprisingly, although each of three precursor pairs tested varied profoundly in their intracellular stability, they were indistinguishable in either T cell stimulation assays, or in the amounts of naturally processed peptides in the APC extracts. Our findings demonstrate that the proteolytic turnover of endogenously synthesized proteins is not directly proportional to the generation of processed antigenic peptide/MHC class I complexes.
内源性合成的细胞蛋白的蛋白水解作用对于加工后的肽/MHC I类复合物在抗原呈递细胞（APC）表面组成性展示以刺激CD8+ T细胞至关重要。然而，正常的蛋白质周转作为加工后肽的来源的程度尚不清楚。为了解决这个问题，我们使用了对内新的N端规则底物，它们在细胞内稳定性方面存在差异，并作为生成肽/MHC I类（OVA257 - 264/Kb或流感核蛋白366 - 374/Db）复合物的前体。令人惊讶的是，尽管测试的三对前体在细胞内稳定性上有很大差异，但在T细胞刺激试验或APC提取物中天然加工肽的量方面，它们并无区别。我们的研究结果表明，内源性合成蛋白的蛋白水解周转与加工后的抗原肽/MHC I类复合物的生成不成正比。
