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

Timo Burster, Bernhard O Boehm

Research output: Contribution to journalReview article

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)227-38
Number of pages12
JournalDiabetes/Metabolism Research and Reviews
Volume26
Issue number4
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Keywords

  • Animals
  • Antigen Presentation
  • Cathepsins
  • Dendritic Cells
  • Desensitization, Immunologic
  • Diabetes Mellitus, Type 1
  • Histocompatibility Antigens Class II
  • Humans
  • Immunologic Factors
  • Lymphocyte Activation
  • Major Histocompatibility Complex
  • Peptide Fragments
  • Proinsulin
  • T-Lymphocytes, Regulatory
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

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