Boulanger, DSM;
Eccleston, RC;
Phillips, A;
Coveney, P;
Elliott, T;
Dalchau, N;
(2018)
A Mechanistic Model for Predicting Cell Surface Presentation of Competing Peptides by MHC Class I Molecules.
Frontiers in Immunology
, 9
, Article 1538. 10.3389/fimmu.2018.01538.
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Abstract
Major histocompatibility complex-I (MHC-I) molecules play a central role in the immune response to viruses and cancers. They present peptides on the surface of affected cells, for recognition by cytotoxic T cells. Determining which peptides are presented, and in what proportion, has profound implications for developing effective, medical treatments. However, our ability to predict peptide presentation levels is currently limited. Existing prediction algorithms focus primarily on the binding affinity of peptides to MHC-I, and do not predict the relative abundance of individual peptides on the surface of antigen-presenting cells in situ which is a critical parameter for determining the strength and specificity of the ensuing immune response. Here, we develop and experimentally verify a mechanistic model for predicting cell-surface presentation of competing peptides. Our approach explicitly models key steps in the processing of intracellular peptides, incorporating both peptide binding affinity and intracellular peptide abundance. We use the resulting model to predict how the peptide repertoire is modified by interferon-γ, an immune modulator well known to enhance expression of antigen processing and presentation proteins.
| Type: | Article |
|---|---|
| Title: | A Mechanistic Model for Predicting Cell Surface Presentation of Competing Peptides by MHC Class I Molecules |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2018.01538 |
| Publisher version: | https://doi.org/10.3389/fimmu.2018.01538 |
| Language: | English |
| Additional information: | Copyright: © 2018 Boulanger, Eccleston, Phillips, Coveney, Elliott and Dalchau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | antigen presentation, major histocompatibility class I, mechanistic model, interferon-γ, peptide competition, abundance |
| 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/10053812 |
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