Processing and presentation of (pro)-insulin in the MHC class II pathway: the generation of antigen-based immunomodulators in the context of type 1 diabetes mellitus
✍ Scribed by Timo Burster; Bernhard O. Boehm
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 194 KB
- Volume
- 26
- Category
- Article
- ISSN
- 1520-7552
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✦ Synopsis
Abstract
Both CD4^+^ and CD8^+^ T lymphocytes play a crucial role in the autoimmune process leading to T1D. Dendritic cells take up foreign antigens and autoantigens; within their endocytic compartments, proteases degrade exogenous antigens for subsequent presentation to CD4^+^ T cells via MHC class II molecules. A detailed understanding of autoantigen processing and the identification of autoantigenic T cell epitopes are crucial for the development of antigen‐based specific immunomodulators. APL are peptide analogues of auto‐immunodominant T cell epitopes that bind to MHC class II molecules and can mediate T cell activation. However, APL can be rapidly degraded by proteases occurring in the extracellular space and inside cells, substantially weakening their efficiency. By contrast, protease‐resistant APL function as specific immunomodulators and can be used at low doses to examine the functional plasticity of T cells and to potentially interfere with autoimmune responses. Here, we review the latest achievements in (pro)‐insulin processing in the MHC class II pathway and the generation of APL to mitigate autoreactive T cells and to activate Treg cells. Copyright © 2010 John Wiley & Sons, Ltd.