Eccleston, RC;
Coveney, PV;
Dalchau, N;
(2017)
Host genotype and time dependent antigen presentation of viral peptides: predictions from theory.
Scientific Reports
, 7
, Article 14367. 10.1038/s41598-017-14415-8.
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Abstract
The rate of progression of HIV infected individuals to AIDS is known to vary with the genotype of the host, and is linked to their allele of human leukocyte antigen (HLA) proteins, which present protein degradation products at the cell surface to circulating T-cells. HLA alleles are associated with Gag-specific T-cell responses that are protective against progression of the disease. While Pol is the most conserved HIV sequence, its association with immune control is not as strong. To gain a more thorough quantitative understanding of the factors that contribute to immunodominance, we have constructed a model of the recognition of HIV infection by the MHC class I pathway. Our model predicts surface presentation of HIV peptides over time, demonstrates the importance of viral protein kinetics, and provides evidence of the importance of Gag peptides in the long-term control of HIV infection. Furthermore, short-term dynamics are also predicted, with simulation of virion-derived peptides suggesting that efficient processing of Gag can lead to a 50% probability of presentation within 3 hours post-infection, as observed experimentally. In conjunction with epitope prediction algorithms, this modelling approach could be used to refine experimental targets for potential T-cell vaccines, both for HIV and other viruses.
| Type: | Article |
|---|---|
| Title: | Host genotype and time dependent antigen presentation of viral peptides: predictions from theory |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-14415-8 |
| Publisher version: | https://doi.org/10.1038/s41598-017-14415-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, IMMUNODEFICIENCY-VIRUS TYPE-1, CYTOTOXIC T-LYMPHOCYTES, CLASS-I BINDING, HIV-1-INFECTED INDIVIDUALS, PROTEASOMAL CLEAVAGE, REPLICATION CAPACITY, DISEASE PROGRESSION, EPITOPE DISCOVERY, ESCAPE MUTATIONS, TAP TRANSPORT |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10034101 |
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