Redox Motif Peptides for Cytolytic CD4+ T Cell Induction
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Solution Overview
Problem
Current strategies for preventing unwanted immune responses against antigens, such as insulin in type 1 diabetes, are inadequate in generating cytolytic CD4+ T cells with sufficient IFN-gamma and sFasL production.
Innovation Solution
Development of novel peptides comprising a tetrapeptide redox motif (Cxx[CST] or [CST]xxC) and an LALEGSLQK epitope sequence, separated by 0 to 5 amino acids, to enhance cytolytic CD4+ T cell generation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional peptides with oxidoreductase motif and MHC class II epitope are used, then immune response prevention is achieved, but cytolytic CD4+ T cell generation with sufficient IFN-gamma and sFasL production is inadequate
Solution Approach 1:
The patent modifies the peptide structure by changing parameters such as adding an N-terminal histidine residue, modifying the oxidoreductase motif sequence, and adjusting the linker region between the motif and epitope. These parameter changes enhance the peptide's ability to generate cytolytic CD4+ T cells with increased IFN-gamma and sFasL production while maintaining immune response prevention
Solution Approach 2:
The invention creates composite peptide structures combining the oxidoreductase motif (Cxx[CST] or [CST]xxC), a linker sequence (0-5 amino acids), and the MHC class II epitope (LALEGSLQK). This composite structure integrates multiple functional elements to simultaneously achieve immune response prevention and enhanced cytolytic T cell generation
2Ease of manufacture
If peptide structure is simplified, then manufacturing ease is improved, but capacity to generate cytolytic CD4+ T cells with increased IFN-gamma and Granzyme B production is reduced
Solution Approach 1:
The patent optimizes peptide parameters by using short amino acid sequences (12-50 residues) with defined motifs, which maintains manufacturing simplicity while achieving enhanced cytolytic function through specific sequence features like the oxidoreductase motif and epitope combination
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The peptides increase IFN-gamma and Granzyme B production in CD4+ T cells, indicating a greater capacity to generate cytolytic CD4+ T cells, potentially effective in treating type 1 diabetes.
Implementation Method 1
WO 2008/017517 describes a new strategy using peptides comprising an MHC class II antigen of a given antigenic protein and an oxidoreductase motif. These peptides convert CD4+ T cells into a cell type with cytolytic properties called cytolytic CD4+ T cells.
Data Source
AI summary
The invention relates to peptides such as HCPYCSLQPLALEGSLQKRG [SEQ ID NO: 26] and their use in the treatment of type 1 diabetes and the generation of cytolytic CD4+ T cell.