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.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Harbige J,Eichmann M,Peakman Mdoi
10.1016/j.jaut.2017.08.001subject
Has Abstractpub_date
2017-11-01 00:00:00pages
12-20eissn
0896-8411issn
1095-9157pii
S0896-8411(17)30389-Xjournal_volume
84pub_type
杂志文章,评审abstract：:CD4(+) IFN-gamma-producing Th1 cells have long been associated with the pathogenesis of many organ-specific autoimmune diseases; however, the observation of disease in mice deficient in molecules involved in Th1 cell differentiation raised the possibility that other effector T cells were responsible for inducing autoi...
journal_title：Journal of autoimmunity
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journal_title：Journal of autoimmunity
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journal_title：Journal of autoimmunity
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pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.2002.0607
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2014.01.025
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2010.07.007
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2012.05.003
更新日期：2012-09-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2015.05.003
更新日期：2015-07-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1997.0134
更新日期：1997-06-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2008.10.003
更新日期：2009-02-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2020.102418
更新日期：2020-03-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2012.07.011
更新日期：2012-12-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1998.0215
更新日期：1998-10-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1997.9998
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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更新日期：2017-07-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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更新日期：2006-08-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1998.0258
更新日期：1999-03-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1003
更新日期：1994-02-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1995.0031
更新日期：1995-06-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(91)90016-6
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(92)90187-u
更新日期：1992-12-01 00:00:00
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1006/jaut.2000.0418
更新日期：2000-09-01 00:00:00
