Dataset Information

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees.

ABSTRACT:

Background

The highly polymorphic genes of the major histocompatibility complex (MHC) class I are involved in defense against viruses and other intracellular pathogens. Although several studies found reduced MHC class I diversity in bonobos in comparison to the closely related chimpanzee, it is unclear if this lower diversity also influences the functional ability of MHC class I molecules in bonobos. Here, we use a bioinformatic approach to analyze the viral peptide binding ability of all published bonobo MHC class I molecules (n =?58) in comparison to all published chimpanzee MHC class I molecules (n =?161) for the class I loci A, B, C and A-like.

Results

We examined the peptide binding ability of all 219 different MHC class I molecules to 5,788,712 peptides derived from 1432 different primate viruses and analyzed the percentage of bound peptides and the overlap of the peptide binding repertoires of the two species. We conducted multiple levels of analysis on the "species"-, "population"- and "individual"-level to account for the characterization of MHC variation in a larger number of chimpanzees and their broader geographic distribution. We found a lower percentage of bound peptides in bonobos at the B locus in the "population"-level comparison and at the B and C loci in the "individual"-level comparison. Furthermore, we found evidence of a limited peptide binding repertoire in bonobos by tree-based visualization of functional clustering of MHC molecules, as well as an analysis of peptides bound by both species.

Conclusion

Our results suggest a reduced MHC class I viral peptide binding ability at the B and C loci in bonobos compared to chimpanzees. The effects of this finding on the immune defense against viruses in wild living bonobos are unclear. However, special caution is needed to prevent introduction and spread of new viruses to bonobos, as their defensive ability to cope with new viruses could be limited compared to chimpanzees.

SUBMITTER: Maibach V

PROVIDER: S-EPMC6327438 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees.

Maibach Vincent V Vigilant Linda L

BMC evolutionary biology 20190110 1

<h4>Background</h4>The highly polymorphic genes of the major histocompatibility complex (MHC) class I are involved in defense against viruses and other intracellular pathogens. Although several studies found reduced MHC class I diversity in bonobos in comparison to the closely related chimpanzee, it is unclear if this lower diversity also influences the functional ability of MHC class I molecules in bonobos. Here, we use a bioinformatic approach to analyze the viral peptide binding ability of al ...[more]

PMID: 30630404

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Project description:Major Histocompatibility Complex (MHC) class I molecules enable cytotoxic T lymphocytes to destroy virus-infected or cancerous cells, thereby preventing disease progression. MHC class I molecules provide a snapshot of the contents of a cell by binding to protein fragments arising from intracellular protein turnover and presenting these fragments at the cell surface. Competing fragments (peptides) are selected for cell-surface presentation on the basis of their ability to form a stable complex with MHC class I, by a process known as peptide optimization. A better understanding of the optimization process is important for our understanding of immunodominance, the predominance of some T lymphocyte specificities over others, which can determine the efficacy of an immune response, the danger of immune evasion, and the success of vaccination strategies. In this paper we present a dynamical systems model of peptide optimization by MHC class I. We incorporate the chaperone molecule tapasin, which has been shown to enhance peptide optimization to different extents for different MHC class I alleles. Using a combination of published and novel experimental data to parameterize the model, we arrive at a relation of peptide filtering, which quantifies peptide optimization as a function of peptide supply and peptide unbinding rates. From this relation, we find that tapasin enhances peptide unbinding to improve peptide optimization without significantly delaying the transit of MHC to the cell surface, and differences in peptide optimization across MHC class I alleles can be explained by allele-specific differences in peptide binding. Importantly, our filtering relation may be used to dynamically predict the cell surface abundance of any number of competing peptides by MHC class I alleles, providing a quantitative basis to investigate viral infection or disease at the cellular level. We exemplify this by simulating optimization of the distribution of peptides derived from Human Immunodeficiency Virus Gag-Pol polyprotein.

Dataset Information

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees.

Background

Results

Conclusion

Publications

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees.

Similar Datasets

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