Regulatory T Cell Epitopes for Targeted Immune Tolerance
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Solution Overview
Problem
Current therapies for autoimmunity, transplantation, and immune responses to therapeutic proteins often rely on broad-based immune cell depleting methods, which are aggressive and vulnerable to opportunistic infections, autoimmune attacks, and cancer, with a need for more targeted and less aggressive approaches to induce immune tolerance.
Innovation Solution
Development of novel regulatory T cell epitope compositions, including polypeptides and pharmaceutical formulations, that selectively engage and activate naturally occurring regulatory T cells to suppress unwanted immune responses, using specific sequences (SEQ ID NOS: 1-73) to induce tolerance in autoimmune diseases, transplantation disorders, and immune reactions to therapeutic proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-based immune cell depleting therapies are used to induce immune tolerance, then immune tolerance is achieved, but the immune system is weakened making subjects vulnerable to opportunistic infections, autoimmune attacks and cancer
Solution Approach 1:
The invention segments the immune system into specific target cells (regulatory T cells) versus non-target cells (other immune cells). By designing epitope compositions that selectively bind to and activate only regulatory T cells through specific HLA molecules, the therapy achieves immune tolerance induction while leaving other immune cells intact and functional, thus avoiding the harmful effects of broad-based depletion
Solution Approach 2:
The invention applies local quality by creating epitope compositions with specific amino acid sequences that are recognized by particular HLA alleles (e.g., HLA-DRB1*04:01, HLA-DRB1*03:01). This specificity ensures that only regulatory T cells expressing these particular HLA molecules are activated, while other immune cells and regulatory T cells with different HLA types remain unaffected, providing targeted immune modulation
2Object-affected harmful factors
If targeted regulatory T cell activation is used to induce immune tolerance, then vulnerability to opportunistic infections is reduced, but the complexity of identifying specific epitopes and HLA specificity increases
Solution Approach 1:
The invention achieves universality by identifying epitope sequences that can bind to multiple HLA alleles within the same supertype (e.g., HLA-DRB1*04:01, *04:05, *04:08 all belong to the HLA-DRB1*04 supertype). A single epitope composition can activate regulatory T cells in patients with different HLA alleles, making the therapy broadly applicable while maintaining targeted activation. This multi-functionality reduces the need for completely customized epitopes for each patient's HLA type
Solution Approach 2:
The invention applies preliminary action by conducting in silico screening and in vitro validation to identify epitope sequences with predicted binding affinity to specific HLA alleles before clinical use. The epitope sequences are designed based on known HLA binding motifs and validated for their ability to activate regulatory T cells in vitro, allowing for rational design and reduction of the complexity of epitope identification
Data Source
AI summary
The present is directed to compositions comprising regulatory T cell epitopes, wherein said epitopes comprise a polypeptide comprising at least a portion of SEQ NOS: 1-73, fragments and/or variants thereof, as well as methods of producing and using the same.