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Design of protease-resistant myelin basic protein-derived peptides by cleavage site directed amino acid substitutions

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Item Type:Article
Title:Design of protease-resistant myelin basic protein-derived peptides by cleavage site directed amino acid substitutions
Creators Name:Burster, T. and Marin-Esteban, V. and Boehm, B.O. and Dunn, S. and Roetzschke, O. and Falk, K. and Weber, E. and Verhelst, S.H. and Kalbacher, H. and Driessen, C.
Abstract:Multiple Sclerosis (MS) is considered to be a T cell-mediated autoimmune disease. An attractive strategy to prevent activation of autoaggressive T cells in MS, is the use of altered peptide ligands (APL), which bind to major histocompatibility complex class II (MHC II) molecules. To be of clinical use, APL must be capable of resisting hostile environments including the proteolytic machinery of antigen presenting cells (APC). The current design of APL relies on cost- and labour-intensive strategies. To overcome these major drawbacks, we used a deductive approach which involved modifying proteolytic cleavage sites in APL. Cleavage site-directed amino acid substitution of the autoantigen myelin basic protein (MBP) resulted in lysosomal protease-resistant, high-affinity binding peptides. In addition, these peptides mitigated T cell activation in a similar fashion as conventional APL. The strategy outlined allows the development of protease-resistant APL and provides a universal design strategy to improve peptide-based immunotherapeutics.
Keywords:Antigen Presentation/Processing, Antigens/Peptides/Epitopes, Autoimmunity, MHC
Source:Biochemical Pharmacology
ISSN:0006-2952
Publisher:Elsevier (The Netherlands)
Volume:74
Number:10
Page Range:1514-1523
Date:15 November 2007
Additional Information:The original publication is available at www.sciencedirect.com
Official Publication:https://doi.org/10.1016/j.bcp.2007.07.037
PubMed:View item in PubMed

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