In silico functional analysis of the human, chimpanzee, and gorilla MHC-A repertoires.

IF 2.9 4区 医学 Q2 GENETICS & HEREDITY
Griffin Kutler Dodd, Can Keşmir
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引用次数: 0

Abstract

T cells recognize peptides displayed on the surface of cells on MHC molecules. Genetic variation in MHC genes alters their peptide-binding repertoire and thus influences the potential immune response generated against pathogens. Both gorillas and chimpanzees show reduced diversity at their MHC class I A (MHC-A) locus compared to humans, which has been suggested to be the result of a pathogen-mediated selective sweep. More specifically, gorillas lack A3 lineage alleles while chimpanzees seem to have lost the A2 lineage. While previous studies showed this using phylogenetic analysis, here, we take an in silico functional approach and use the peptide-MHC binding prediction software NetMHCpan to examine the peptide-binding repertoires of common human, chimpanzee, and gorilla MHC-A molecules. We find that both gorillas and chimpanzees lack the A02 peptide binding specificity (supertype) despite gorillas being expected to have this specificity since they kept the A2 lineage. Additionally, we show that human MHC molecules with the A02 specificity bind fewer virus-derived peptides than other MHC molecules. We also do not find differential presentation of self-peptides by the A02 supertype, making the purpose of maintaining this specificity in high frequencies in the human population unclear. Taken together, we hypothesize that poor presentation of viral peptides by A02 supertype MHC molecules could have resulted in a selective sweep in chimpanzees and/or gorillas, though we could not identify a specific virus that may have caused this sweep.

人类、黑猩猩和大猩猩MHC-A基因库的计算机功能分析。
T细胞识别MHC分子上显示在细胞表面的肽。MHC基因的遗传变异改变了它们的肽结合库,从而影响了对病原体产生的潜在免疫反应。与人类相比,大猩猩和黑猩猩的MHC I类A (MHC-A)位点的多样性都有所降低,这被认为是病原体介导的选择性清除的结果。更具体地说,大猩猩缺乏A3谱系等位基因,而黑猩猩似乎失去了A2谱系。虽然之前的研究使用系统发育分析证明了这一点,但在这里,我们采用了一种硅功能方法,并使用肽- mhc结合预测软件NetMHCpan来检查常见的人类,黑猩猩和大猩猩MHC-A分子的肽结合谱。我们发现大猩猩和黑猩猩都缺乏A02肽结合特异性(超型),尽管大猩猩被认为具有这种特异性,因为它们保留了A2谱系。此外,我们发现与其他MHC分子相比,具有A02特异性的人MHC分子结合的病毒衍生肽较少。我们也没有发现A02超型自身肽的差异表现,这使得在人群中维持这种高频率特异性的目的不清楚。综上所述,我们假设A02超型MHC分子的病毒肽的不佳呈现可能导致黑猩猩和/或大猩猩的选择性扫描,尽管我们无法确定可能导致这种扫描的特定病毒。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunogenetics
Immunogenetics 医学-免疫学
CiteScore
6.20
自引率
6.20%
发文量
48
审稿时长
1 months
期刊介绍: Immunogenetics publishes original papers, brief communications, and reviews on research in the following areas: genetics and evolution of the immune system; genetic control of immune response and disease susceptibility; bioinformatics of the immune system; structure of immunologically important molecules; and immunogenetics of reproductive biology, tissue differentiation, and development.
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