Borrelia MHC Multimer Panels for Stable T Cell Detection

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Solution Overview

Problem

The short half-life of peptide-MHC-T cell receptor complexes and weak binding of MHC-peptide monomers pose challenges for labeling specific T cells and employing them therapeutically, limiting the effectiveness of existing MHC multimers.

Innovation Solution

Development of MHC multimers comprising multiple MHC-peptide complexes associated with multimerization domains, specifically designed for Borrelia antigenic peptides, to enhance binding affinity and interaction longevity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If MHC-peptide monomers are used for labeling T cells, then the labeling can be performed, but the binding affinity is weak and the half-life is short

Engineering Contradiction:

Improvebinding affinityVSAvoidhalf-life of MHC-peptide-T cell receptor complex

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent combines multiple MHC-peptide monomers into multimeric complexes (dimers, trimers, tetramers, pentamers, hexamers, heptamers, or octamers) to increase binding affinity. The multimerization domain allows multiple MHC-peptide units to associate, creating a cooperative binding effect that overcomes the weak binding of individual monomers and extends the interaction half-life with T cell receptors.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates composite MHC multimer structures combining multiple MHC-peptide complexes with a multimerization domain. This composite architecture integrates the antigen-presenting function of MHC-peptide monomers with the stabilizing and affinity-enhancing properties of the multimerization domain, resulting in a hybrid structure with improved binding characteristics.

Inventive Principle:

Principle #40Composite materials

2Reliability

If MHC multimers are designed with multiple MHC-peptide complexes, then binding affinity is enhanced, but device complexity increases

Engineering Contradiction:

Improvebinding affinityVSAvoidstructure of MHC multimer

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The multimerization domain serves multiple functions simultaneously: it acts as a structural scaffold for assembling MHC-peptide monomers, provides a basis for affinity maturation, enables stable complex formation, and facilitates interaction with T cell receptors. This multi-functionality reduces the need for separate structural and functional components, thereby managing complexity while enhancing binding affinity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention optimizes parameters such as the number of MHC-peptide monomers per multimer, the type of multimerization domain, and the spacing/orientation of monomers to achieve optimal binding affinity. By systematically varying these parameters, the patent identifies configurations that provide high affinity without excessive structural complexity.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250382335A1Panel comprising Borrelia MHC multimers

Publication Date: 2025.12.18 IMMUDEX APS

AI summary

Disclosed herein is a panel comprising one or more MHC multimers; and a panel comprising one or more pools of MHC multimers, wherein each pool comprises one or more MHC multimers; wherein said MHC multimers comprise an antigenic peptide P derived from a Borrelia antigenic polypeptide selected from the group consisting of OppA, DbpA, FlhF, FlaB and P37-42; as well as uses thereof in the detection of Borrelia-specific T cells and the diagnosis, treatment and monitoring of Borrelia disease in an individual.