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A mechanistic model for predicting cell surface presentation of competing peptides by MHC class I molecules

A mechanistic model for predicting cell surface presentation of competing peptides by MHC class I molecules
A mechanistic model for predicting cell surface presentation of competing peptides by MHC class I molecules
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.
1664-3224
1-15
Boulanger, Denise
c226ad99-9c9a-485a-b480-42fb8799120f
Eccleston, Ruth C.
0c8c63b3-538e-471a-8429-a181344198dd
Phillips, Andrew
e6eaf60a-0ef7-4337-9f21-ae1945a81a3d
Coveney, Peter V.
9ffa84bf-09e1-40f7-a104-8bba23708915
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Dalchau, Neil
8e948fc2-9e6c-4275-85a2-cc7c13858f04
Boulanger, Denise
c226ad99-9c9a-485a-b480-42fb8799120f
Eccleston, Ruth C.
0c8c63b3-538e-471a-8429-a181344198dd
Phillips, Andrew
e6eaf60a-0ef7-4337-9f21-ae1945a81a3d
Coveney, Peter V.
9ffa84bf-09e1-40f7-a104-8bba23708915
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Dalchau, Neil
8e948fc2-9e6c-4275-85a2-cc7c13858f04

Boulanger, Denise, Eccleston, Ruth C., Phillips, Andrew, Coveney, Peter V., Elliott, Timothy and Dalchau, Neil (2018) A mechanistic model for predicting cell surface presentation of competing peptides by MHC class I molecules. Frontiers in Immunology, 9, 1-15. (doi:10.3389/fimmu.2018.01538).

Record type: Article

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.

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Accepted/In Press date: 21 June 2018
e-pub ahead of print date: 5 July 2018

Identifiers

Local EPrints ID: 421920
URI: https://eprints.soton.ac.uk/id/eprint/421920
ISSN: 1664-3224
PURE UUID: b7bc1e0a-4779-430c-884a-26800b98e364
ORCID for Denise Boulanger: ORCID iD orcid.org/0000-0003-1000-7313
ORCID for Timothy Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 10 Jul 2018 16:30
Last modified: 14 Mar 2019 01:46

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