Chimeric Peptides for Broad HLA-DR Binding

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

The challenge lies in predicting and selecting antigenic peptides that can effectively stimulate T-helper responses across a wide range of HLA-DR molecules due to the polymorphism of MHC molecules, which affects binding regions and recognition, limiting the universality of vaccine epitopes.

Innovation Solution

Synthesis of chimeric peptides with specific amino acid sequences that adapt to defined formulas, allowing strong binding to multiple allelic forms of HLA-DR molecules, including HLA-DR1, HLA-DR2, HLA-DR3, HLA-DR4, HLA-DR7, HLA-DR8, and HLA-DR11, and potentially binding to HLA-DP and HLA-DQ molecules, thereby inducing T-helper responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If epitopes are selected for specific HLA-DR molecules, then the immune response stimulation is effective for that specific molecule, but the universality across different HLA-DR polymorphisms is limited

Engineering Contradiction:
Improveuniversality of vaccine epitopesVSAvoidbinding effectiveness
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies universality by designing epitopes with conserved amino acid motifs that can bind to multiple HLA-DR polymorphic molecules. The epitopes are engineered to recognize common structural features across different HLA-DR alleles rather than relying on allele-specific interactions, enabling a single epitope to function across diverse genetic backgrounds.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent employs parameter changes by systematically varying specific amino acid residues at key positions within the epitope sequence to optimize binding affinity across different HLA-DR molecules. By modifying parameters such as hydrophobicity, charge, and steric properties at anchor positions, the epitopes achieve broad compatibility while maintaining reliable binding.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If chimeric Thd peptides are designed to modulate stimulating potency, then the binding capacity with MHC molecules is increased, but the complexity of peptide design and selection increases

Engineering Contradiction:
Improvebinding capacity with MHC moleculesVSAvoidpeptide design complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the epitope into distinct functional regions: anchor residues that bind to the MHC groove, contact residues that interact with the T-cell receptor, and spacer regions that provide structural flexibility. This modular approach allows independent optimization of each segment for binding affinity and immunogenicity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs composite materials by creating chimeric epitopes that combine conserved amino acid sequences from different pathogenic sources. These composite epitopes integrate binding motifs from multiple origins to achieve both high MHC affinity and broad T-cell recognition across different HLA types.

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

The synthesized peptides demonstrate strong binding capabilities to multiple HLA-DR allelic forms and induce effective T-helper and cytotoxic T responses, providing a broader spectrum of immune response coverage.

Implementation Method 1

the ThL recognize, through specific receptors (CTR) situated on its surface, complexes formed between Class II MHC molecules and antigenic peptides

Methodology Applied
Scientific EffectAntigen-antibody binding: Absorption (physical)

Data Source

PatentEP1978026B1T-helper antigenic determinant (THD) peptides
Publication Date: 2011.03.16 PROYECTO DE BIOMEDICINA CIMA
  • EP1978026B1 patent drawingFigure 1
  • EP1978026B1 patent drawingFigure 2~3
  • EP1978026B1 patent drawingFigure 4

AI summary

The invention relates to a chimeric peptide, which can bind to at least one allelic form of the HLA-DR molecule. The invention also relates to a pharmaceutical composition containing said peptide, as well as to the different uses of same.