Characterising the immunopeptidome in hepatitis B
type: CreativeWork
description: Characterising the immunopeptidome in hepatitis B Hepatitis B (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. There is presently no cure for HBV, and treatment options aim to reduce the risk of liver related complications and HCC. Immunotherapies have not been successful in achieving the long-term immune control required for functional cure. The display of HBV-derived peptides on major histocompatibility class I (MHC-class I, human leukocyte antigen (HLA) class I in humans) molecules on the cell surface is crucial to mount antiviral immune cell mediated responses. Immunogenic peptides are generated and selected via the HLA class I antigen presentation pathway (APP). Within this pathway, two homologous molecules tapasin and tapasin-related molecule TAPBPR optimize the peptide repertoire presented on HLA class I on the cell surface. TAPBPR is involved in both loading optimal peptides and preventing sub-optimal peptides from loading (filtering) and has been shown to restrict the peptide repertoire on HLA -A, -B and -C molecules. By using an immunopeptidomics approach, I aimed to identify novel HBV-derived epitopes presented on HLA class I molecules which could be utilised in new peptide-based immunotherapies, to induce broad T cell responses and achieve functional cure. I hypothesised that depletion of TAPBPR would alter the HBV peptide repertoire presented to immune cells. I then subsequently explored whether recombinant TAPBPR can be utilised to render HBV infected cells more immunogenic. I first conducted a comprehensive literature review on HLA presented HBV peptides which revealed that the vast majority of HBV-derived peptides characterised to date are restricted to HLA-A allotypes and are not representative of HBV endemic regions. Furthermore, the majority of studies over the last two decades have used computational methods to identify novel HLA class I presented HBV peptides. Based on the information obtained, cell lines overexpressing si…
abstract: Characterising the immunopeptidome in hepatitis B Hepatitis B (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. There is presently no cure for HBV, and treatment options aim to reduce the risk of liver related complications and HCC. Immunotherapies have not been successful in achieving the long-term immune control required for functional cure. The display of HBV-derived peptides on major histocompatibility class I (MHC-class I, human leukocyte antigen (HLA) class I in humans) molecules on the cell surface is crucial to mount antiviral immune cell mediated responses. Immunogenic peptides are generated and selected via the HLA class I antigen presentation pathway (APP). Within this pathway, two homologous molecules tapasin and tapasin-related molecule TAPBPR optimize the peptide repertoire presented on HLA class I on the cell surface. TAPBPR is involved in both loading optimal peptides and preventing sub-optimal peptides from loading (filtering) and has been shown to restrict the peptide repertoire on HLA -A, -B and -C molecules. By using an immunopeptidomics approach, I aimed to identify novel HBV-derived epitopes presented on HLA class I molecules which could be utilised in new peptide-based immunotherapies, to induce broad T cell responses and achieve functional cure. I hypothesised that depletion of TAPBPR would alter the HBV peptide repertoire presented to immune cells. I then subsequently explored whether recombinant TAPBPR can be utilised to render HBV infected cells more immunogenic. I first conducted a comprehensive literature review on HLA presented HBV peptides which revealed that the vast majority of HBV-derived peptides characterised to date are restricted to HLA-A allotypes and are not representative of HBV endemic regions. Furthermore, the majority of studies over the last two decades have used computational methods to identify novel HLA class I presented HBV peptides. Based on the information obtained, cell lines overexpressing si…
author: Sinharay, Ricky
language: eng
keywords: hepatitis B, MHC class I antigen presentation, TAPBPR
license: https://www.repository.cam.ac.uk/bitstreams/172284ef-2c21-4689-90b6-4a23a52963ca/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-06-24
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.120735