Surface-Bound Peptide-MHC Arrays for Immunodominant Peptide Identification

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Solution Overview

Problem

Current methods for analyzing peptide interactions with major histocompatibility complex (MHC) are limited in accurately identifying immunodominant peptides in vivo, relying on computer algorithms that may not reflect biological relevance and requiring extensive empirical verification and sequencing.

Innovation Solution

A surface-bound peptide-MHC system is synthesized in situ, allowing for the simultaneous analysis of multiple peptides to identify immunodominant ones by precisely recapitulating the in vivo peptide-MHC assembly, using a digital micromirror device to create spatially ordered arrays and eliminate the need for empirical verification and sequencing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If computer algorithms are used to predict immunodominant peptides, then prediction capability is improved, but biological relevance deteriorates

Engineering Contradiction:

Improveprediction capabilityVSAvoidbiological relevance

Core Design Contradiction:

Extent of automationVSReliability

Solution Approach 1:

The invention creates physical copies of peptide-MHC assemblies on a surface, where each spotted assembly replicates the in vivo structure. This allows direct empirical testing of peptide immunodominance rather than relying on algorithmic predictions, thereby improving biological relevance while maintaining automation through high-throughput spotting and analysis capabilities

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The system allows the peptide-MHC assemblies to naturally interact with immune cells without requiring external manipulation or interpretation algorithms. The assemblies self-present peptides to T-cells, and the immune response directly indicates immunodominance, eliminating the need for computer prediction algorithms and improving biological relevance

Inventive Principle:

Principle #25Self-service

2Reliability

If empirical verification is performed to confirm peptide relevance, then reliability is improved, but time consumption deteriorates

Engineering Contradiction:

Improvepeptide relevance verificationVSAvoidverification time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The invention performs preliminary action by pre-assembling peptide-MHC complexes and spotting them onto a surface before introducing immune cells. This pre-preparation allows multiple peptides to be simultaneously ready for testing, enabling parallel empirical verification that reduces total verification time while maintaining reliability through direct biological testing

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The verification process is segmented into multiple parallel assays, where different peptide-MHC assemblies are tested simultaneously on the surface with different immune cell populations. This segmentation allows comprehensive empirical verification of multiple peptides at once, reducing overall verification time while maintaining rigorous reliability standards

Inventive Principle:

Principle #1Segmentation

3Loss of information

If sequencing is performed to identify peptide sequences, then information accuracy is improved, but cost and time deterioration

Engineering Contradiction:

Improvepeptide sequence identification accuracyVSAvoidsequencing time

Core Design Contradiction:

Loss of informationVSLoss of time

Solution Approach 1:

The invention performs preliminary action by synthesizing peptides with known, predetermined sequences before assembling them with MHC molecules. This eliminates the need for subsequent sequencing to identify peptide sequences, as the sequences are already characterized. This approach maintains information accuracy while eliminating the time-consuming sequencing step

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention extracts the sequencing step entirely from the workflow by using pre-synthesized peptides with known sequences. By taking out this unnecessary step, the process reduces both time consumption and cost while maintaining complete information accuracy about peptide sequences through the established synthesis records

Inventive Principle:

Principle #2Taking out (Extraction)

4Productivity

If multiple peptides are analyzed simultaneously, then productivity is improved, but system complexity deteriorates

Engineering Contradiction:

Improvepeptide analysis throughputVSAvoidarray system complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The invention segments the analysis system into standardized, modular components: peptide synthesis modules, MHC assembly modules, surface spotting modules, and immune cell analysis modules. Each module handles a specific function, allowing multiple peptides to be analyzed simultaneously through parallel processing while managing complexity through modular design and standardized protocols

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS11583575B2MHC-bound peptide arrays and methods of use thereof

Publication Date: 2023.02.21 ROCHE SEQUENCING SOLUTIONS INC

AI summary

The disclosure provides compositions comprising at least one assembly comprising a peptide and a major histocompatibility complex (MHC), wherein the peptide is an integral component of the MHC, wherein the peptide is attached to a surface at its C-terminus through a linker and wherein the peptide is synthesized on the surface. In certain embodiments, the compositions comprise a plurality of assemblies in a spatially-ordered array. The disclosure provides methods for making and using these compositions.