Celiac Disease Epitope Peptides for Diagnostic Specificity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic and therapeutic methods for celiac disease (CeD) are inadequate due to the difficulty in identifying effective T cell epitopes, leading to delayed diagnosis and management challenges, and existing assays have low sensitivity and cumbersome procedures.
Innovation Solution
Identification of a new 9-mer T cell epitope associated with CeD, specifically the sequence PYPQQQQPY, and its deamidated forms, which can be used to develop peptides that interact with HLA-DQ2.5 and HLA-DQ2.2 molecules, enhancing diagnostic and therapeutic options.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing diagnostic assays based on TG2 antibodies or anti-gluten peptide antibodies are used, then disease specificity is improved, but sensitivity and ease of operation deteriorate due to low sensitivity and cumbersome procedures
Solution Approach 1:
The patent changes the diagnostic parameter from detecting antibodies (TG2 antibodies or anti-gluten peptide antibodies) to detecting T cell epitopes with specific amino acid sequences (e.g., PYPQQQQPY and its deamidated forms). This parameter change enables the use of simpler, more sensitive detection methods such as ELISA or flow cytometry with peptide pools, thereby improving ease of operation while maintaining disease specificity.
Solution Approach 2:
The patent creates simplified diagnostic copies by using synthetic peptide versions of the epitopes (e.g., PYPQQQQPY) that can be detected by T cell responses. These peptide copies serve as proxies for the complex antibody detection methods, enabling easier and more sensitive diagnosis through direct detection of T cell epitope recognition.
2Reliability
If current diagnostic methods are used, then diagnostic capability is maintained, but diagnosis time increases due to delayed diagnosis
Solution Approach 1:
The patent enables preliminary diagnosis by directly detecting T cell epitope recognition patterns that are characteristic of celiac disease. By using peptide pools containing the epitopes (e.g., PYPQQQQPY and related sequences) and detecting T cell responses in vitro, the diagnosis can be made earlier in the disease course, before significant intestinal damage occurs, thereby reducing diagnosis time while maintaining reliability.
3Reliability
If gluten exclusion diet is used as treatment, then therapeutic effect is achieved, but adherence difficulty increases due to incredible difficulty to manage and adhere to
Solution Approach 1:
The patent enables feedback-based treatment monitoring by detecting T cell responses to specific gluten peptides. By measuring T cell epitope recognition (e.g., to PYPQQQQPY) in patient samples, clinicians can monitor whether the gluten exclusion diet is effectively controlling the disease. This feedback mechanism allows for personalized treatment adjustments and improves patient adherence by providing clear guidance on treatment effectiveness.
Solution Approach 2:
The patent changes the therapeutic monitoring parameter from clinical symptoms to immunological markers (T cell epitope recognition). This allows for objective measurement of treatment response and enables earlier detection of flare-ups, making adherence monitoring more straightforward and improving overall treatment management.
4Reliability
If new T cell epitope PYPQQQQPY is identified and used, then diagnostic specificity and therapeutic potential are improved, but device complexity increases due to need for new peptide-based assays
Solution Approach 1:
The patent creates universal diagnostic tools by developing peptide pools that contain multiple epitopes (e.g., PYPQQQQPY and related sequences) that can be detected by a single assay system. This multi-functional approach allows the same peptide-based assay to detect various T cell responses associated with celiac disease, simplifying the overall diagnostic workflow while maintaining high specificity.
Solution Approach 2:
The patent uses synthetic peptide copies of the epitopes (e.g., PYPQQQQPY) as simplified diagnostic targets. These peptide copies can be incorporated into standard ELISA or flow cytometry assays, avoiding the need for complex new diagnostic devices while enabling highly specific detection of T cell epitope recognition patterns.
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 new T cell epitope provides improved diagnostic specificity and therapeutic potential by targeting gluten-reactive T cells, potentially leading to earlier and more accurate diagnosis and effective treatment of CeD.
Implementation Method 1
The immunogenicity of gluten peptides is greatly augmented through post-translational modification by the enzyme transglutaminase 2 (TG2), which by deamidation converts certain glutamine residues (Q) to glutamate (E)
Data Source
AI summary
The present invention provides a peptide comprising an epitope, e.g. a T cell epitope, that comprises the amino acid sequence PYPQQQQPY or an epitope, e.g. a T cell epitope, that comprises the amino acid sequence PYPQQQQPY in which one or more of the Q residues is replaced by an E residue, wherein the peptide is not more than 50 amino acids in length. Conjugates or complexes comprising said peptides and an MHC molecule are also provided, together with various therapeutic and diagnostic uses of said peptides and complexes.