Recombinant MHC Class II Alpha1 Domain Polypeptide for Inflammatory Disease
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Solution Overview
Problem
Current treatments for autoimmune and inflammatory disorders, such as multiple sclerosis, are not sufficiently effective in managing inflammatory responses and tissue damage, despite recent progress.
Innovation Solution
A recombinant MHC class II α1 domain polypeptide is developed, conjugated with a MOG-35-55 peptide via a linker sequence, which enhances stability and efficacy in treating inflammatory diseases by inhibiting CD74 expression and reducing inflammatory cell infiltration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If an MHC class II α1 domain polypeptide is used to treat inflammatory disease, then immune response is modulated, but the stability of the secondary structure is insufficient and efficacy is limited
Solution Approach 1:
The patent combines the MHC class II α1 domain with an antigenic peptide (MOG-35-55) through a linker sequence to create a fusion polypeptide. This merging of two functional elements—the MHC domain for immune modulation and the antigenic peptide for structural stability—results in a construct that simultaneously achieves both improved secondary structure stability and enhanced therapeutic efficacy in treating inflammatory diseases.
Solution Approach 2:
The invention creates a composite polypeptide structure consisting of the MHC class II α1 domain, a linker sequence, and an antigenic peptide. This composite construction allows the different domains to contribute their respective properties: the MHC domain provides immune modulation capability while the antigenic peptide component enhances the stability of the secondary structure, resolving the contradiction between reliability and structural stability.
2Reliability
If conventional treatments are used for autoimmune disorders, then some therapeutic effect is achieved, but the treatments are not sufficiently effective in managing inflammatory responses and tissue damage
Solution Approach 1:
The recombinant polypeptide works by presenting antigenic peptides to T-cells in a controlled manner, thereby preemptively modulating the immune response before it can cause significant tissue damage. This preliminary anti-action approach prevents the harmful inflammatory cascade from fully developing, addressing both the insufficiency of conventional treatments and the issue of tissue damage.
Solution Approach 2:
The MHC class II α1 domain acts as an intermediary that presents antigenic peptides to T-cells, mediating the immune response in a controlled fashion. This intermediary function allows for precise modulation of the immune system's activity, achieving better effectiveness in managing inflammatory responses while reducing harmful tissue damage compared to conventional treatments.
Data Source
AI summary
Recombinant polypeptides comprising a DRα1 domain, an antigenic peptide, and a linker sequence are disclosed. The linker sequence comprises a first glycine-serine spacer, a thrombin cleavage site and a second glycine-serine spacer. Further disclosed are pharmaceutical compositions comprising the recombinant polypeptides, methods of treating inflammatory disease using said pharmaceutical compositions, and expression constructs comprising nucleic acids that encode the recombinant polypeptides.