PLP-Derived Peptides for MHC Binding and T-Cell Presentation
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Solution Overview
Problem
Current therapies for multiple sclerosis (MS) are often associated with adverse effects and are poorly tolerated, with no known cure, highlighting a need for alternative treatments that effectively manage the symptoms and progression of the disease.
Innovation Solution
Identification and use of peptides derived from proteolipid protein (PLP) that can bind directly to MHC molecules without antigen processing, allowing for presentation to T-cells and potentially inducing tolerance, thereby treating or preventing demyelinating diseases like MS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current MS therapies are used to treat multiple sclerosis, then disease progression can be managed, but adverse effects increase and tolerability decreases
Solution Approach 1:
The invention segments the myelin basic protein antigen into smaller peptide fragments (e.g., MBP 23-34, MBP 84-96) that can be separately administered. This segmentation allows targeting of specific T-cell clones involved in the autoimmune response while avoiding activation of broader immune responses, thereby maintaining disease management effectiveness while reducing adverse effects compared to whole protein or non-specific immunosuppressants
Solution Approach 2:
The patent uses peptide intermediaries that bind to MHC molecules to mediate the immune response. These peptide-MHC complexes act as intermediaries that present specific antigenic determinants to T-cells, inducing tolerance without triggering the harmful immune responses associated with current therapies. The peptides serve as safe intermediaries between the antigen and the immune system
2Reliability
If peptides are designed to bind directly to MHC molecules without antigen processing, then presentation to T-cells is enhanced, but peptide selection and optimization becomes more complex
Solution Approach 1:
The invention performs preliminary computational analysis to predict which peptide sequences will bind effectively to specific MHC molecules before synthesis and testing. By pre-screening peptide candidates in silico based on their predicted MHC binding affinity and stability, the researchers can prioritize synthesis of the most promising peptides, thereby enhancing T-cell presentation efficiency while reducing the overall complexity of peptide selection and optimization
Solution Approach 2:
The patent systematically varies peptide parameters such as amino acid sequence, length, and MHC binding affinity to optimize T-cell presentation. By changing these parameters in a controlled manner and evaluating their effects on MHC binding and T-cell recognition, the invention identifies optimal peptide configurations that enhance presentation efficiency without requiring exhaustive screening of all possible peptide variants
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 PLP-derived peptides can induce tolerance and reduce immune responses associated with MS, offering a potentially more effective and tolerable treatment option by targeting specific T-cell clones and reducing disease progression.
Implementation Method 1
capable of binding to an MHC molecule in vitro and being presented to a T cell without antigen processing
Data Source
AI summary
There is provided a peptide which is capable of binding to an MHC molecule in vitro and being presented to a T cell without antigen processing (i.e. an apitope) which peptide comprises all or a portion of the following proteolipid protein (PLP) peptides: PLP 36-61: HE ALTGTEKLIET YF SKN YQD YEYLI (SEQ ID NO. 1) PLP 179-206: TWTTCQSIAFPSKTSASIGSLCA-DARMY (SEQ ID NO. 2) PLP 207-234: GVLPWNAFPGKVCGSNLLSICKTAEFQM (SEQ ID NO. 3). There is also provided the use of such a peptide in a pharmaceutical composition and a method to treat and/or prevent a disease using such a peptide.