Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: implications for determinant spreading

McLaughlin, Kerry A., Richardson, Carolyn C., Williams, Stefan , Bonifacio, Ezio, Morgan, Diana, Feltbower, Richard G., Powell, Michael, Rees Smith, Bernard, Furmaniak, Jadwiga and Christie, Michael R. (2015) Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: implications for determinant spreading. Clinical Immunology, 160 (2). pp. 226-236. ISSN 1521-6616

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Item Type:Article
Item Status:Live Archive

Abstract

Diversification of autoimmunity to islet autoantigens is critical for progression to Type 1 diabetes. B-cells participate in diversification by modifying antigen processing, thereby influencing which peptides are presented to T-cells. In Type 1 diabetes, JM antibodies are associated with T-cell responses to PTP domain peptides. We investigated whether this is the consequence of close structural alignment of JM and PTP domain determinants on IA-2. Fab fragments of IA-2 antibodies with epitopes mapped to the JM domain blocked IA-2 binding of antibodies that recognise epitopes in the IA-2 PTP domain. Peptides from both the JM and PTP domains were protected from degradation during proteolysis of JM antibody:IA-2 complexes and included those representing major T-cell determinants in Type 1 diabetes. The results demonstrate close structural relationships between JM and PTP domain epitopes on IA-2. Stabilisation of PTP domain peptides during proteolysis in JM-specific B-cells may explain determinant spreading in IA-2 autoimmunity.

Keywords:Immunology, Type 1 diabetes, Autoimmunity, bmjgoldcheck, NotOAChecked
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18188
Deposited On:03 Aug 2015 15:31

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