Peptide Binding to CD1 Molecules for NKT Cell Activation
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Solution Overview
Problem
Existing therapies for tumors, chronic autoimmune and inflammatory diseases, and conditions associated with intracellular pathogens are limited by the inability to target specific antigens, leading to non-specific immune responses and immunosuppression, while therapeutic proteins often elicit immune reactions.
Innovation Solution
Development of peptides that selectively bind to CD1a, CD1b, and CD1c proteins to activate NKT cells, allowing antigen-specific immune responses and modulating NKT cell activity through specific binding and activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides are designed to activate NKT cells through CD1 binding, then immune response specificity is improved, but device complexity increases due to peptide design and screening requirements
Solution Approach 1:
The patent employs parameter changes by systematically varying peptide sequences and analyzing their binding properties to CD1 molecules. Through computational algorithms and high-throughput screening, peptide parameters (amino acid composition, sequence length, hydrophobicity) are optimized to achieve specific binding to CD1a, CD1b, or CD1c while activating NKT cells. This resolves the contradiction by transforming the complex design problem into a systematic parameter optimization process.
Solution Approach 2:
The patent introduces computational algorithms and high-throughput screening assays as intermediaries between the desired immune response and the actual peptide design. These intermediary tools enable systematic evaluation of peptide-CD1 binding affinity and NKT cell activation potential, reducing the complexity of direct experimental trial-and-error approaches while improving the reliability of immune response specificity.
2Reliability
If therapeutic proteins are administered, then treatment efficacy is improved, but immune reactions against the therapeutic protein increase
Solution Approach 1:
The patent extracts and modifies the immunogenic epitopes from therapeutic proteins by identifying and removing or mutating the peptide sequences that bind to CD1 molecules and activate NKT cells. Through systematic analysis of therapeutic protein sequences and identification of CD1-binding epitopes, the harmful immunogenic components are extracted and eliminated while preserving the therapeutic function of the protein.
Solution Approach 2:
The patent applies parameter changes to therapeutic protein sequences by introducing amino acid substitutions, deletions, or additions that alter the peptide structure to prevent binding to CD1 molecules. This modifies the immunogenic parameters of the therapeutic protein, reducing NKT cell activation while maintaining the protein's therapeutic efficacy.
3Reliability
If conventional NKT cell activation by lipids or glycolipids is used, then activation reliability is improved, but adaptability to peptidic epitopes is limited
Solution Approach 1:
The patent fundamentally changes the parameter of antigen structure by demonstrating that CD1 molecules can present peptidic epitopes in addition to their conventional lipid or glycolipid ligands. Through identification and characterization of peptidic sequences that bind to CD1a, CD1b, and CD1c and activate NKT cells, the patent expands the ligand space from lipids/glycolipids to include peptides, thereby increasing adaptability while maintaining activation reliability.
Solution Approach 2:
The patent establishes the multi-functionality of CD1 molecules by showing they can present both conventional lipid/glycolipid antigens and peptidic epitopes to activate NKT cells. This universality allows a single CD1 molecule to recognize diverse antigen types, significantly expanding the adaptability of NKT cell activation mechanisms while preserving the reliability of the activation response.
Data Source
AI summary
The invention relates to a method to determine, based on the activation level of NKT cells, the capacity of a peptidic epitope to selectively bind to CD1a, CD1b and/or CD1c proteins, a corresponding method to increase or decrease the selective binding of the peptidic epitope to CD1a, CD1b and/or CD1c proteins by modifying the epitope or its flanking regions, the corresponding modified epitopes and the activated NKT cells or parts thereof obtainable by these methods.