AI Article Synopsis
- Diversification of autoimmunity to islet autoantigens is essential for the development of Type 1 diabetes, with B-cells altering antigen processing to impact T-cell peptide presentation.
- In Type 1 diabetes, the presence of JM antibodies correlates with T-cell responses to certain peptides, and the study examines the structural alignment between JM and PTP domain determinants on IA-2.
- Results show that JM domain antibodies can block the binding of antibodies to the PTP domain, leading to the stabilization of key T-cell determinant peptides in B-cells, which may drive the spread of autoimmunity.
Article 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.
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| http://dx.doi.org/10.1016/j.clim.2015.06.002 | DOI Listing |
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