Discriminating self from nonself with short peptides from large proteomes
Discriminating self from nonself with short peptides from large proteomes
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DOI：
10.1007/s00251-004-0691-0
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发表时间：
2004-08-01
期刊：
影响因子：
3.2
通讯作者：
Kesmir, C
中科院分区：
文献类型：
--
作者：
Burroughs, NJ;de Boer, RJ;Kesmir, C
我们研究了9个氨基酸的肽（9聚体），通常用于MHC I类呈递是否足够独特的自我：非自我歧视。人类蛋白质组包含28，783种蛋白质，包括10（7）种不同的9聚体。列举各种微生物的不同9聚体，我们发现平均重叠，i.show外源肽也存在于人类自身中的概率约为0.2%。当使用较短的肽时，这种自身：非自身重叠增加，e.show 6-聚体为30%，7-聚体为3%。预测所有的9聚体，预计将被切割的免疫蛋白酶体和TAP易位，我们发现，约25%的自我和非自我9聚体被成功地处理。对于HLA-A*0201和HLA-A*0204等位基因，我们预测了来自每个蛋白质组的经加工的9聚体中的哪些预期被呈递在MHC上。这两个等位基因都倾向于将加工的9聚体呈递给未加工的9聚体，并且都对呈递外源肽有小的偏好。因为来自每个9聚体的许多氨基酸结合MHC，并且因此不暴露于TCR，抗原呈递似乎涉及信息的显著丢失。我们的研究结果表明，这是不是因为HLA分子是相当具体的情况。去除两个锚残基从每个肽，我们发现，这些暴露的7-聚体的自我：非自我重叠类似于9-聚体。总之，在MHC I类呈递中使用的9聚体倾向于携带足够的信息来检测自身肽中的非自身肽。
We studied whether the peptides of nine amino acids (9-mers) that are typically used in MHC class I presentation are sufficiently unique for self:nonself discrimination. The human proteome contains 28,783 proteins, comprising 10(7) distinct 9-mers. Enumerating distinct 9-mers for a variety of microorganisms we found that the average overlap, i.show $132#e., the probability that a foreign peptide also occurs in the human self, is about 0.2%. This self:nonself overlap increased when shorter peptides were used, e.show $132#g., was 30% for 6-mers and 3% for 7-mers. Predicting all 9-mers that are expected to be cleaved by the immunoproteasome and to be translocated by TAP, we find that about 25% of the self and the nonself 9-mers are processed successfully. For the HLA-A*0201 and HLA-A*0204 alleles, we predicted which of the processed 9-mers from each proteome are expected to be presented on the MHC. Both alleles prefer to present processed 9-mers to nonprocessed 9-mers, and both have small preference to present foreign peptides. Because a number of amino acids from each 9-mer bind the MHC, and are therefore not exposed to the TCR, antigen presentation seems to involve a significant loss of information. Our results show that this is not the case because the HLA molecules are fairly specific. Removing the two anchor residues from each presented peptide, we find that the self:nonself overlap of these exposed 7-mers resembles that of 9-mers. Summarizing, the 9-mers used in MHC class I presentation tend to carry sufficient information to detect nonself peptides amongst self peptides.