Recognition of HIV-1 Peptides by Host CTL Is Related to HIV-1 Similarity to Human Proteins
Recognition of HIV-1 Peptides by Host CTL Is Related to HIV-1 Similarity to Human Proteins
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DOI：
10.1371/journal.pone.0000823
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发表时间：
2007-09-05
期刊：
影响因子：
3.7
通讯作者：
Mullins, James I.
中科院分区：
文献类型：
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作者：
Rolland, Morgane;Nickle, David C.;Mullins, James I.
背景资料。虽然人类免疫缺陷病毒1型(HIV-1)特异性细胞毒T淋巴细胞优先靶向病毒蛋白质组的特定区域，但HIV-1有助于免疫识别的特征尚不清楚。一种假说是，HIV和人类蛋白之间的相似性会影响宿主的免疫反应，即病毒和宿主多肽之间的相似性可能会阻止对某些HIV表位的反应。方法/主要调查结果。我们分析了HIV-1与人类蛋白质组的相似程度。来自2001年HIV-1B共有序列的蛋白质被解剖成重叠的k-MERS，然后根据人类蛋白质组的非冗余数据库进行探测，以识别高度相似的片段。我们测试了HIV-1与宿主编码多肽的相似性与HIV感染者的免疫识别之间的关系，发现HIV的免疫原性可以部分地受到与宿主蛋白质组序列的相似性的调节。Elispot对跨越整个病毒蛋白质组的多肽的反应在314个人中进行了评估，结果显示出一种趋势，表明与宿主蛋白质组的相似性与识别频率之间存在反向关系。此外，对一组30名艾滋病毒感染者对944个重叠多肽的反应进行了分析，这些多肽代表了广泛的HIV-1B Nef变异体，确认具有反应性表位的多肽与宿主的相似性明显低于那些未被识别的多肽。结论/意义。我们的结果表明，在人类蛋白质中很少表达的抗原基序可能代表了更多的免疫原性CTL靶标，而不是针对宿主。这一观察结果可以为设计更有效的艾滋病毒免疫原提供指导，因为缺乏宿主样特征的序列可能提供更好的免疫反应性。
Background. While human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. Methodology/Principal Findings. We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. Conclusions/Significance. Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.