NDLI: Most nuclear systemic autoantigens are extremely disordered proteins: implications for the etiology of systemic autoimmunity

Content Provider	PubMed Central
Author	Carl, Philip L. Temple, Brenda Rs Cohen, Philip L.
Abstract	Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies in normal individuals.
Related Links	http://dx.doi.org/10.1186/ar1832
Starting Page	1360
File Format	PDF
ISSN	14786354
e-ISSN	14786362
Journal	Arthritis Research & Therapy
Issue Number	6
Volume Number	7
Language	English
Publisher	BioMed Central
Publisher Date	2005-01-01
Access Restriction	Open
Rights Holder	BioMed Central
Subject Keyword	Immunology Immunology and Allergy Rheumatology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology

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