Many peptide fragments of alien antigens are homologous with host proteins, thus canalizing T-cell responses.
Many peptide fragments of alien antigens are homologous with host proteins, thus canalizing T-cell responses.
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外来抗原的许多肽片段与宿主蛋白同源，从而引导 T 细胞反应。
DOI：
10.1073/pnas.88.8.3065
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发表时间：
1991
影响因子：
11.1
通讯作者：
Susumu Ohno
中科院分区：
文献类型：
--
作者：
Susumu Ohno
这个世界上所有的蛋白质都是按照同样的规则构建的。因此，两个完全不相关的蛋白质平均每500个残基共有30个相同的三肽、两个四肽和一个五肽。考虑到这一点，221个残基长的流感病毒血凝素II（IVHA-II），作为外来抗原的代表，与三种不同的蛋白质代表宿主：533个残基长的鸡c-src蛋白激酶（劳斯肉瘤病毒的细胞癌基因的c-src产物），595个残基长的人雌激素受体，和585个残基长的人血清白蛋白进行了比较。在三种宿主蛋白中的一种或另一种中也发现了IVHA-II的43个三肽、两个四肽和一个五肽。IVHA-II的6个区域（9-22个残基长）中，与其宿主寡肽相同的寡肽成簇，被定义为“宿主同源”区域，其余区域被称为“非自身”或“病原体特异性”区域。由于宿主蛋白质的总数远远超过三个，因此宿主同源区域无疑被低估了，而IVHA-II中只有一两个区域必须保持真正的病原体特异性。然而，寡肽分析两个已知的T细胞应答引发肽片段和一个已知的惰性肽片段的病毒和疟疾原虫很容易揭示后者是一个主机同源区。在两个已知的T细胞反应引发肽片段中，一个比另一个更不自我。毫不奇怪，更多的非自身片段引起辅助性T细胞反应的个人不同的主要组织相容性复合体单倍型，而较少的非自身片段引起细胞毒性T细胞反应，仅从HLA-A2人类个体。
All proteins of this world are constructed in compliance with the same rule. Accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. With this in mind, the 221-residue-long influenza virus hemagglutinin II (IVHA-II), as a representative of alien antigens, was compared with three diverse proteins representing the host: 533-residue-long chicken c-src protein kinase (c-src product of the cellular oncogene of Rous sarcoma virus), 595-residue-long human estrogen receptor, and 585-residue-long human serum albumin. Forty-three tripeptides, two tetrapeptides, and one pentapeptide of IVHA-II were also found in one or the other of the three host proteins. Six regions of IVHA-II (9-22 residues long) in which oligopeptides were clustered that were identical to their host oligopeptides were defined as "host-homologous" regions, and the remaining regions were called "nonself" or "pathogen-specific" regions. Because the total number of host proteins is vastly more than three, host-homologous regions were no doubt underestimated, while only one or two regions of IVHA-II must remain as truly pathogen-specific. Nevertheless, oligopeptide analysis of two known T-cell response-eliciting peptide fragments and one known inert peptide fragment of a virus and a malarial protozoan readily revealed the latter to be a host-homologous region. Of the two known T-cell response-eliciting peptide fragments, one was more nonself than the other. Not surprisingly, the more nonself fragment elicited helper T-cell response from individuals of diverse major histocompatibility complex haplotypes, whereas the less nonself fragment elicited cytotoxic T-cell response only from HLA-A2 human individuals.