Victoria Brentville
T cell repertoire to citrullinated self-peptides in healthy humans is not confined to the HLA-DR SE alleles; targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy
Brentville, Victoria; Symonds, Peter; Cook, Katherine W.; Daniels, Ian; Pitt, Tracy; Gijon, Mohamed; Vaghela, Poonam; Xue, Wei; Shah, Sabaria; Metheringham, Rachael L.; Durrant, Lindy G.
Authors
Peter Symonds
Katherine W. Cook
Ian Daniels
Tracy Pitt
Mohamed Gijon
Poonam Vaghela
Wei Xue
Sabaria Shah
Rachael L. Metheringham
Lindy G. Durrant
Contributors
Lindy Durrant
Project Leader
Abstract
Post-translational modifications are induced in stressed cells which cause them to be recognised by the immune system. One such modification is citrullination where the positive charged arginine is modified to a neutral citrulline. We demonstrate most healthy donors show an oligoclonal CD4 response in vitro to at least one citrullinated vimentin or enolase peptide. Unlike rheumatoid arthritis patients, these T cell responses were not restricted by HLA-DRB1 shared epitope (SE) alleles, suggesting they could be presented by other MHC-II alleles. As HLA-DP is less polymorphic than HLA-DR, we investigated whether the common allele, HLA-DP4 could present citrullinated epitopes. The modification of arginine to citrulline enhanced binding of the peptides to HLA-DP4 and induced high frequency CD4 responses in HLA-DP4 transgenic mouse models. Our previous studies have shown that tumours present citrullinated peptides restricted through HLA-DR4 which are good targets for anti-tumour immunity. In this study we show that citrullinated vimentin and enolase peptides also induced strong anti-tumour immunity (100% survival, p
Citation
Brentville, V., Symonds, P., Cook, K. W., Daniels, I., Pitt, T., Gijon, M., …Durrant, L. G. (2019). T cell repertoire to citrullinated self-peptides in healthy humans is not confined to the HLA-DR SE alleles; targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy. OncoImmunology, 8(5), https://doi.org/10.1080/2162402X.2019.1576490
Journal Article Type | Article |
---|---|
Acceptance Date | Dec 11, 2018 |
Online Publication Date | Feb 20, 2019 |
Publication Date | Feb 20, 2019 |
Deposit Date | Jan 7, 2019 |
Publicly Available Date | Feb 21, 2020 |
Journal | OncoImmunology |
Print ISSN | 2162-4011 |
Electronic ISSN | 2162-402X |
Publisher | Taylor & Francis Open |
Peer Reviewed | Peer Reviewed |
Volume | 8 |
Issue | 5 |
Article Number | e1576490 |
DOI | https://doi.org/10.1080/2162402X.2019.1576490 |
Keywords | Immunology; Immunology and Allergy; Oncology |
Public URL | https://nottingham-repository.worktribe.com/output/1446751 |
Publisher URL | https://www.tandfonline.com/doi/full/10.1080/2162402X.2019.1576490 |
Additional Information | This is an Accepted Manuscript of an article published by Taylor & Francis in OncoImmunology on 12 Feb 2019, available online: https://doi.org/10.1080/2162402X.2019.1576490. |
Files
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