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New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease?

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New insights into non-conventional epitopes as T cell targets : The missing link for breaking immune tolerance in autoimmune disease? / Harbige, James; Eichmann, Martin; Peakman, Mark.

In: Journal of Autoimmunity, 10.08.2017.

Research output: Contribution to journalArticle

Harvard

Harbige, J, Eichmann, M & Peakman, M 2017, 'New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease?', Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2017.08.001

APA

Harbige, J., Eichmann, M., & Peakman, M. (2017). New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease? Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2017.08.001

Vancouver

Harbige J, Eichmann M, Peakman M. New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease? Journal of Autoimmunity. 2017 Aug 10. https://doi.org/10.1016/j.jaut.2017.08.001

Author

Harbige, James ; Eichmann, Martin ; Peakman, Mark. / New insights into non-conventional epitopes as T cell targets : The missing link for breaking immune tolerance in autoimmune disease?. In: Journal of Autoimmunity. 2017.

Bibtex Download

@article{49f1e667a54d4229b1e0a114f794ece5,
title = "New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease?",
abstract = "The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases. In this review article, we discuss current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. We contextualise these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. Non-conventional epitopes have the potential to act as tolerance breakers or disease drivers in type 1 diabetes, prompting a timely re-evaluation of models of a etiopathogenesis. Future studies are required to elucidate the disease-relevance of a range of potential non-germline epitopes and their relationship to the natural peptide repertoire.",
author = "James Harbige and Martin Eichmann and Mark Peakman",
year = "2017",
month = aug,
day = "10",
doi = "10.1016/j.jaut.2017.08.001",
language = "English",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "ACADEMIC PRESS INC",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - New insights into non-conventional epitopes as T cell targets

T2 - The missing link for breaking immune tolerance in autoimmune disease?

AU - Harbige, James

AU - Eichmann, Martin

AU - Peakman, Mark

PY - 2017/8/10

Y1 - 2017/8/10

N2 - The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases. In this review article, we discuss current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. We contextualise these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. Non-conventional epitopes have the potential to act as tolerance breakers or disease drivers in type 1 diabetes, prompting a timely re-evaluation of models of a etiopathogenesis. Future studies are required to elucidate the disease-relevance of a range of potential non-germline epitopes and their relationship to the natural peptide repertoire.

AB - The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases. In this review article, we discuss current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. We contextualise these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. Non-conventional epitopes have the potential to act as tolerance breakers or disease drivers in type 1 diabetes, prompting a timely re-evaluation of models of a etiopathogenesis. Future studies are required to elucidate the disease-relevance of a range of potential non-germline epitopes and their relationship to the natural peptide repertoire.

UR - http://www.scopus.com/inward/record.url?scp=85028358560&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2017.08.001

DO - 10.1016/j.jaut.2017.08.001

M3 - Article

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -

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