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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

Victoria Brentville

Peter Symonds

Katherine W. Cook

Ian Daniels

Tracy Pitt

Mohamed Gijon

Poonam Vaghela

Wei Xue

Sabaria Shah

Rachael L. Metheringham

Lindy G. Durrant



Contributors

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

Journal Article Type Article
Publication Date Feb 20, 2019
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
APA6 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
DOI https://doi.org/10.1080/2162402X.2019.1576490
Keywords Immunology; Immunology and Allergy; Oncology
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.

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