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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