Thimet oligopeptidase and the stability of MHC class I epitopes in macrophage cytosol
Thimet oligopeptidase and the stability of MHC class I epitopes in macrophage cytosol
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DOI：
10.1006/bbrc.1999.0251
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发表时间：
1999-02-24
影响因子：
3.1
通讯作者：
de Camargo, ACM
中科院分区：
文献类型：
--
作者：
Portaro, FCV;Gomes, MD;de Camargo, ACM
在这项研究中，我们研究了一类蛋白酶体产生的寡肽的命运，将它们暴露于巨噬细胞的粗细胞质或纯化的重组硫硫寡肽酶。在已知序列的蛋白酶体产物中有MHC I类表位，随机选择其中13个作为推定底物。令人惊讶的是，我们的结果清楚地表明，无论是被纯化的酶还是被粗的巨噬细胞细胞质，大多数肽都很差或不能被降解。这些抗水解的多肽作为竞争性抑制剂对硫寡肽酶表现出高亲和力。尽管我们的数据不允许预测特定肽是否会被降解，但很可能是结构特征排除了细胞质中MAC I类肽的稳定性，这可能对抗原呈递的优化库选择有影响。(C) 1999学术出版社。
In this study we investigated the fate of a class of proteasome-generated oligopeptides, exposing them to the crude cytosol of macrophages or to the purified recombinant thimet oligopeptidase. Among the proteasome products of known sequences are MHC class I epitopes, 13 of which were randomly chosen to be used as putative substrates. Surprisingly, our results clearly showed that the majority of the peptides were poorly or not degraded, either by the purified enzyme or by the crude macrophage cytosol. The peptides, which were resistant to hydrolysis, displayed high affinity for the thimet oligopeptidase as competitive inhibitors. Regardless of the fact that our data do not allow prediction of whether or not a specific peptide would be degraded, it seems very likely that the structural features, which rule out the stability of the MAC class I peptides in the cytosol, may have implications in an optimized repertoire selection for antigen presentation. (C) 1999 Academic Press.