MHC Multimers for Borrelia T Cell Detection
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Solution Overview
Problem
The short half-life of peptide-MHC-T cell receptor ternary complexes and weak binding of MHC monomers pose challenges for labeling specific T cells and employing MHC-peptide complexes in therapeutic and vaccine applications.
Innovation Solution
Development of MHC multimers, which are complexes with increased affinity and half-life, formed by covalently or non-covalently attaching multiple copies of MHC-peptide complexes to a multimerization domain, such as dimers, tetramers, pentamers, dextramers, and streptamers, to enhance interaction stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If MHC monomers are used for labeling T cells, then the labeling process is simple, but the binding affinity and half-life are insufficient
Solution Approach 1:
The patent combines multiple MHC-peptide complexes with a multimerization domain to form MHC multimers. This merging approach increases the binding affinity and half-life while maintaining the essential function of T cell labeling, effectively resolving the contradiction between simplicity and reliability.
Solution Approach 2:
The patent creates composite structures by attaching MHC-peptide complexes to multimerization domains such as streptavidin, antibodies, or dextran. These composite materials exhibit enhanced stability and binding characteristics compared to simple MHC monomers, addressing the reliability issue while preserving usability.
2Reliability
If multiple copies of MHC-peptide complexes are attached to form multimers, then the binding affinity and half-life are improved, but the structural complexity increases
Solution Approach 1:
The patent introduces multimerization domains as intermediary structures that facilitate the assembly of multiple MHC-peptide complexes. These intermediaries (such as streptavidin, antibodies, or dextran) provide a standardized platform for multimer formation, reducing the overall structural complexity compared to direct multimer assembly.
Solution Approach 2:
The patent segments the MHC multimer structure into distinct functional modules: the MHC-peptide complex units and the multimerization domain. This segmentation allows for independent optimization of each component and simplifies the overall design and manufacturing process while achieving high binding affinity.
3Measurement precision
If MHC multimers are used for T cell detection, then the detection sensitivity is improved, but the manufacturing complexity increases
Solution Approach 1:
The patent employs preliminary action by pre-forming the multimerization domain structure before attaching the MHC-peptide complexes. This approach simplifies manufacturing by allowing the complex assembly process to occur in a controlled, stepwise manner rather than attempting to assemble complete multimers from individual components simultaneously.
Solution Approach 2:
The patent utilizes parameter changes by adjusting the stoichiometry and composition of the multimerization domain to optimize both detection sensitivity and manufacturability. By varying parameters such as the number of MHC complexes per multimer and the type of multimerization domain used, the system achieves high detection precision while maintaining reasonable manufacturing complexity.
Data Source
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AI summary
Novel compounds carrying ligands capable of binding to counter receptors on relevant target cells are disclosed. The compounds possess a number of advantageous features, rendering them very suitable for a wide range of applications, including use as detection systems, detection of relevant target cells as well as a number of other methods. In particular, novel MHC complexes comprising one or more MHC molecules containing one or more Borrelia derived peptides are disclosed. The possibility of presenting to the target cells a plurality of MHC-peptide complexes makes the MHC complexes according to the present invention an extremely powerful tool e.g. in the field of therapy and diagnosis. The invention generally relates to the sample-mounted use of MHC complexes and MHC multimers. Also comprised by the invention is the field of therapy and vaccine, including therapeutic/vaccine methods and therapeutic/vaccine compositions.