Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading.
McLaughlin, KA, Richardson, CC, Williams, S et al. (7 more authors)
(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
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.
Metadata
Item Type:
Article
Authors/Creators:
McLaughlin, KA
Richardson, CC
Williams, S
Bonifacio, E
Morgan, D
Feltbower, RG
Powell, M
Smith, BR
Furmaniak, J
Christie, MR
Copyright, Publisher and Additional Information:
This article is available under the terms of the Creative Commons Attribution License (CC BY).
Keywords:
Type 1 diabetes; Autoantibody; Monoclonal antibody; Epitope; Determinant spreading
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)