MR1-Ligand Multimeric Complexes for MAIT Cell Detection

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Solution Overview

Problem

Current methods for identifying and monitoring MAIT cells are limited by the inability to precisely determine the MR1-restricted antigens and TCR antigen specificity, leading to challenges in understanding MAIT cell biology and their protective mechanisms.

Innovation Solution

Development of MR1-ligand subunits and multimeric complexes that bind to MAIT cell TCRs, allowing for the labeling, identification, and characterization of MAIT cells, as well as the modulation of their activity through agonistic or antagonistic roles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods are used to identify and monitor MAIT cells, then general T cell detection is possible, but precise determination of MR1-restricted antigens and TCR antigen specificity is not achieved

Engineering Contradiction:

Improvedetection precision of MAIT cellsVSAvoidinformation on MR1-restricted antigens and TCR antigen specificity

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent introduces MR1-ligand multimeric complexes as intermediary reagents that specifically bind to MAIT cell TCRs. These complexes serve as mediators between the detection system and MAIT cells, enabling precise identification through flow cytometry or other detection methods while preserving information about antigen specificity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs multimeric complexes (tetramers, decamers, etc.) of MR1-ligand structures to enhance binding affinity and detection sensitivity. By changing the oligomeric state from monomeric to multimeric forms, the detection precision for MAIT cells is significantly improved while maintaining antigen specificity information.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If MR1-ligand multimeric complexes are developed for specific MAIT cell detection, then detection precision is improved, but device complexity increases

Engineering Contradiction:

Improvedetection precision of MAIT cellsVSAvoidcomplexity of immunological reagents

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The detection system is segmented into distinct functional components: MR1 heavy chain, β2-microglobulin light chain, specific ligands (6-formylpterin, rRL-6-HM), and multimeric assembly structures. This segmentation allows for modular construction and standardization of detection reagents, managing complexity through systematic organization.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The MR1-ligand multimeric complexes serve multiple functions: they specifically bind MAIT cell TCRs, enable flow cytometry detection, provide antigen specificity information, and can be used for both research and clinical diagnostics. This multi-functionality reduces the need for multiple separate reagents.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Manufacturing precision

If multimeric complexes of MR1-ligand are used for MAIT cell detection, then identification accuracy is improved, but manufacturing complexity increases

Engineering Contradiction:

Improveaccuracy of MAIT cell identificationVSAvoidease of producing multimeric complexes

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The MR1-ligand complexes are pre-assembled into stable multimeric structures (tetramers, decamers) during manufacturing, before use in detection assays. This preliminary assembly ensures consistent binding properties and detection accuracy, while the standardized protocols simplify the manufacturing process.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The multimeric complexes are constructed from composite components: MR1 heterodimers (heavy chain + β2-microglobulin) combined with specific ligands (6-formylpterin or rRL-6-HM) in defined stoichiometric ratios. This composite structure provides both structural stability and functional specificity.

Inventive Principle:

Principle #40Composite materials

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

Enables accurate detection and monitoring of MAIT cells, facilitating the assessment of the adaptive cellular immune response and potential therapeutic interventions for conditions associated with aberrant MAIT cell activity.

Implementation Method 1

MR1-ligand subunits and multimeric complexes that bind to MAIT cell TCRs, allowing for the labeling, identification, and characterization of MAIT cells

Methodology Applied

Scientific EffectAntigen-receptor binding:

Data Source

PatentUS10011602B2Immunological reagents and uses therefor

Publication Date: 2018.07.03 UNIVERSITY OF MELBOURNE

AI summary

The present invention provides a ligand which binds to MR1 wherein said binding results in binding of the MR1 to MAIT cells.