MHC Class Ib Molecules for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Current treatments for autoimmune diseases and cancers often rely on non-specific immune suppression, leading to severe side effects and opportunistic infections, while cancer immunotherapies are hindered by immunosuppressive mechanisms, highlighting the need for targeted, antigen-specific immune modulation.
Innovation Solution
Human MHC class Ib molecules, such as HLA-G, are used to induce antigen-specific tolerance by eliminating cytotoxic T cells or inducing regulatory T cells, and agents that block MHC class Ib molecule binding to their receptors are employed to modulate immune responses, allowing for targeted suppression or enhancement of immune reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-specific immune suppression is used to treat autoimmune diseases and cancers, then immune responses are suppressed, but severe side effects and opportunistic infections occur
Solution Approach 1:
The patent segments the immune system into antigen-specific components, using MHC class Ib molecules to selectively target and suppress only the immune responses against specific autoantigens or tumor antigens, rather than suppressing the entire immune system. This allows treatment of autoimmune diseases and cancers while preserving immunity against pathogens.
Solution Approach 2:
The invention applies local quality by creating antigen-specific immunosuppression through MHC class Ib/peptide complexes that act locally on specific T cell populations recognizing particular antigens. This localized approach suppresses harmful immune responses against self-antigens or tumor antigens while leaving other immune functions intact.
2Reliability
If conventional MHC Ia molecules are used to induce immune responses, then antigen-specific immune reactions are initiated, but non-specific immune suppression is required which causes harmful side effects
Solution Approach 1:
The patent inverts the conventional approach by using MHC class Ib molecules instead of MHC class Ia molecules. While MHC class Ia typically induces immune responses, MHC class Ib molecules are employed to induce antigen-specific tolerance and suppress immune responses, achieving the opposite effect with the same antigen-specificity mechanism.
3Object-affected harmful factors
If targeted antigen-specific immune modulation is implemented, then side effects are reduced, but complexity of immune targeting increases
Solution Approach 1:
The patent uses MHC class Ib molecules as intermediary structures that naturally present peptides to T cells with high specificity. By loading these molecules with target antigens, the system achieves precise immune targeting without requiring complex delivery mechanisms or engineered T cell receptors, simplifying the overall approach to antigen-specific immunomodulation.
Data Source
AI summary
The present invention relates to therapeutical uses of non-classical major histocompatibility complex (MHC), also known as MHC class Ib molecules in combination with defined peptides. The invention more specifically relates to targeted immunomodulatory effects of defined peptides in combination with proteins comprising one or more domains of a non-classical MHC class Ib molecule or in combination with molecules that interfere with the interaction of MHC class Ib molecules and their receptors. The invention also relates to methods of producing such proteins, pharmaceutical compositions comprising the same, as well as their uses for treating medical conditions in which antigen-specific immune reactions are beneficial, including cancer and infectious diseases, or harmful, including autoimmune diseases, organ/tissue rejection, immune reactions towards pharmaceutical compounds or reproductive disorders. Moreover, as the invention reveals a novel mode of action for MHC class Ib molecules during antigen-specific tolerance induction, it also relates to methods for interfering with this mechanism in situation where induction of antigen-specific immune tolerance is wanted, but physiologically prevented by said mechanism.